NAME OF THE COURSE M.S.

NAME OF THE SUBJECT OBSTETRICS AND GYNAECOLOGY

ADMISSION YEAR MAY 2017

ACADEMIC YEAR 2017-2020

PREVALENCE OF IRON DEFICIENCY ANEMIA IN PREGNANCY AND RESPONSE TO ORAL IRON

AND PARENTERAL IRON TREATMENT

1
PREVALENCE OF IRON DEFICIENCY ANEMIA IN PREGNANCY AND RESPONSE TO ORAL
IRON AND PARENTERAL IRON TREATMENT

A Dissertation submitted to

Maharashtra University of Health Sciences, Nashik

For the degree of

M.S. OBSTETRICS AND GYNAECOLOGY
MAY 2020

2
TABLE OF CONTENTS

SR.NO CONTENT PAGE.NO

1. INTRODUCTION 8

2. AIMS AND OBJECTIVES 12

3. REVIEW OF LITERATURE 13

4. MATERIALS AND METHODS 54

5. RESULTS AND ANALYSIS 58

6. DISCUSSION 72

7. CONCLUSION 78

8. SUMMARY 79

9. BIBLIOGRAPHY 80

10. ANNEXURES 94

10.1 DATA COLLECTION PROFORMA 94

10.2 CONSENT PROFORMA 96

10.3 KEY TO MASTER CHART 99

10.4 MASTER CHART 101

3
LIST OF TABLES USED IN REVIEW OF LITERATURE

SERIAL TABLES PAGE NO.

A WORLD HEALTH ORGANISATION (2002) 16
DEGREE OF ANEMIA
B INDIAN COUNSIL OF MEDICAL RESEARCH 17
DEGREE OF ANEMIA
C WORLD HEALTH ORGANISATION (2000) 17
DEGREE OF ANEMIA
D WORLD HEALTH ORGANISATION (2011) 18
CUT OFF VALUES FOR ANEMIA IN PREGNANCY
E BRITISH SOCIETY FOR HAEMATOLOGY (2011) 18
CUT OFF VALUES FOR ANEMIA IN PREGNANCY
F HEMOGLOBIN VALUE ADJUSTMENT AT SEA LEVEL 19

G PREVALENCE OF IRON DEFICIENCY ANEMIA IN PREGNANCY IN INDIA 20

(NFHS-4)- 2015 -2016

H IRON REQUIREMENT IN PREGNANCY 24

I IMPACT OF PREGNANCY ON VARIOUS HEMATOLOGICAL 33

PARAMETERS AND CARDIAC SYSTEM
J STAGES OF DEVELOPMENT OF IRON DEFICIENCY ANEMIA 37
K ASSESSMENT OF IDA 38
L DIFFERENTIAL DIAGNOSIS OF IDA 40
M RECOMMENDATIONS OF VARIOUS NATIONAL PROGRAMMES FOR 44
PROPHYLAXIS IN PREGNANCY

4
 LIST OF IMAGES

SERIAL IMAGE PAGE.NO

I. WORLD HEALTH ORGANISATION 20

PREVALENCE OF IRON DEFICIENCY ANEMIA (2011)

II. NATIONAL FAMILY HEALTH SURVEY -4 (2015-2016) 21

PREVALENCE OF IRON DEFICIENCY ANEMIA

5
LIST OF TABLES IN OBSERVATION AND RESULTS

SERIAL NO. TABLE

1. DISTRIBUTION OF CASES

2. DISTRIBUTION OF STUDY SUBJECTS ACCORDING TO AGE GROUP

3. DISTRIBUTION OF STUDY SUBJECTS ACCORDING TO GRAVIDA STATUS

4. DISTRIBUTION OF STUDY SUBJECTS ACCORDING TO GESTATIONAL AGE

5. DISTRIBUTION OF STUDY SUBJECTS ACCORDING TO ACCORDING TO SIGNS AND

SYMPTOMS

6. DISTRIBUTION OF STUDY SUBJECTS ACCORDING TO HB ELECTROPHORESIS STATUS

7. DISTRIBUTION OF STUDY SUBJECTS ACCORDING TO IRON DEFICIENCY ANEMIA

8. PREVALENCE OF IRON DEFICIENCY AMONG DIFFERENT PARAMETERS STUDIED

9. VARIOUS HAEMATOLOGICAL PARAMETER CHANGES IN BOTH THE GROUPS

10. VARIOUS COMPLICATIONS / SIDEEFFECTS

11. REQUIREMENT OF BLOOD TRANSFUSION IN BOTH THE GROUPS

6
LIST OF CHARTS IN OBSERVATION AND RESULTS

TABLE NO. TITLE.

1. DISTRIBUTION OF CASES

2. DISTRIBUTION OF STUDY SUBJECTS ACCORDING TO AGE GROUP

3. DISTRIBUTION OF STUDY SUBJECTS ACCORDING TO GRAVIDA STATUS

4. DISTRIBUTION OF STUDY SUBJECTS ACCORDING TO GESTATIONAL AGE

5. DISTRIBUTION OF STUDY SUBJECTS ACCORDING TO ACCORDING TO SIGNS AND

SYMPTOMS

6. DISTRIBUTION OF STUDY SUBJECTS ACCORDING TO HB ELECTROPHORESIS STATUS

7. DISTRIBUTION OF STUDY SUBJECTS ACCORDING TO IRON DEFICIENCY ANEMIA

8. VARIOUS HAEMATOLOGICAL PARAMETER CHANGES IN BOTH THE GROUPS

9. VARIOUS COMPLICATIONS/ SIDE EFFECTS IN BOTH THE GROUPS *

10. VARIOUS COMPLICATIONS / SIDEEFFECTS IN BOTH THE GROUPS **

11. REQUIREMENT OF BLOOD TRANSFUSION IN BOTH THE GROUPS

7
 INTRODUCTION

Iron deficiency affects a significant part of the population in nearly every country in the
world even more in developing countries like India. The prevalence is even more amongst
pregnant women. The major reasons for high prevalence are poor socioeconomic status,
illiteracy ,multiple pregnancies, grand multiparas, chronic untreated illnesses, infections and
infestations ,lack of awareness , ANC visits to hospital at later stages when anemia has already
been set , poor follow up in hospital , poor compliance for medications, dietary factors , food
taboos along increased needs during pregnancy and dilutional anemia in second half of
pregnancy play a major role in high prevalence in developing countries like India . Pregnant
women are the major target population of health care system in India as the burden of disease
has impact on both mother and child as well. Various treatment modalities and national
programmes have been implemented and updated to decrease the burden of iron deficiency
anemia in pregnancy , still the prevalence remains high.

World Health Organization (WHO)/World Health Statistics data shows that 40.1% of
pregnant women worldwide were anemic in 2016. The condition is severe in Southeast Asian
countries where about 50% of all global maternal deaths are due to anemia and to it India
contributes to about 80% of the maternal death due to anaemia in South Asia n countries.(1)(2)

According to National Family Health Survey – 4 (2015-2016 ) in India , prevalence of

anemia in pregnancy is 50% ,although prevalence has reduced from 58% NHFS-3 (2005-06) to
50% , value remains high. Prevalence in state of Maharashtra , Rajasthan ,Gujrat, Uttar
Pradesh, Punjab still remains > 40% whereas in kerala , Jammu and Kashmir ,eastern states it is
20-39.9%(3). (4).

As per the global report (nutrition) 2016, india ranked 170 / 185 countries in terms of
anemia prevalence in women.

Programmes for the prevention of iron deficiency, particularly iron supplementation

for pregnant women, are under way in 90 of 112 countries that reported to WHO in 1992(5).

8
Iron deficiency Anemia in pregnancy can cause not only maternal morbidity and mortality but
serious health implications on growing fetus predisposing it to IUGR. Throughout pregnancy,
iron deficiency anemia adversely affects the maternal and fetal well-being, and is related to
high chances of maternal morbidity and fetal death. Affected mothers often have breathing
difficulties, fainting, tiredness, palpitations, and sleep difficulties . (6) severe anemia leads
to chronic cardiac failure . Post-partum cognitive impairment and behavioral difficulties were
also reported(7)(8)(9) Adverse perinatal outcomes include intrauterine growth retardation,
prematurity, and low birth weight, all with significant mortality risks, particularly in the
developing world were noted .(10)(11)(12) Iron deficiency during the first trimester, has a
serious bad impact on growth of fetus than anemia later in pregnancy(13)(14).

Considering the above fact , we need to implement better treatment plans to reduce
prevalence of the disease in country

The standard prophylaxis and treatment in majority of the countries is oral iron (OI ),
blood transfusion is reserved in severe or emergency cases. However, blood transfusion is
unreliable in the treatment .Blood transfusion has its own hazards, like transfusion of wrong
blood and transmission of infections like HIV, hepatitis, CMV, HBsAg and anaphylaxis. Thus,
there is a requirement for a safe and effective alternative to oral iron and blood transfusion in
the treatment of iron deficiency anemia which can prevent unnecessary and unindicated blood
transfusion and can take care of moderate degree of anemia and patients especially in
countries like India where majority of patients get poor health care at primary level because of
poor follow up, non compliance , timely diagnosis of anemia and lot of side effects of oral iron
supplied free at government institutes. Iron dextran, the first parenteral iron used, has a
serious life threatening side effect like anaphylaxis and hence use is discourged . Iron sucrose
was then discovered as a parenteral iron that could be safe and effective.

Iron sucrose's first known use was in Europe in 1949, but it was not used in US medicine
until November 2000(13). It replaced iron dextran, which had been in use in the US since the
1900s, as a treatment for iron deficiency. Iron sucrose complex is used intravenously for
correction of IDA and has less side effects and various Clinical trials and the history of the use

9
of iron sucrose worldwide have established the safety and efficacy of iron sucrose for
treatment of patients with IDA; it is metabolically available very quickly after administration
and is safe, convenient, and more effective than intramuscular iron therapy in the treatment of
IDA during pregnancy.(14). The intravenous iron sucrose therapy can replace blood transfusion
in antenatal period and postnatal period also for moderate IDA, as there are various adverse
reactions associated with blood transfusion (15).

Therapy with iron sucrose avoids the risk of hemo transfusional infections, incompatible
hemotransfusions, and immunocompromising effect of hemotransfusion, and is affordable The
WHO has stated that transfusion should be considered only for conditions for which there is
failure of other treatment options or other treatment options are contraindicated, Blood
transfusion gives rise to Hb temporarily, and is a symptomatic management of anemia. It
cannot cure iron deficiency from root and restore iron balance, hence, it is not a rational
approach to the IDA and should be transfusion be reserved for acute emergency cases of
anemia like blood loss .

Various studies have done to demonstrate efficacy of parenteral iron in reducing the number of
blood transfusions on such study from American college of obstetrics and gynaecology says

“Intravenous iron sucrose is an effective method of treating IDA in pregnant women with
minimal side effects. These results, as well as our previous report associating intravenous iron
sucrose with decreased PRBC transfusion, demonstrate the potential of this therapy to treat
IDA and decrease rates of allogenic blood transfusion. We recommend additional studies be
conducted to show the correlation between iron sucrose treatment and incidence of blood
transfusion in pregnant women.”(16).

Iron sucrose dramatically reduce maternal morbidity and give better

neurodevelopmental functions in newborn and improve the quality of life of mother overall.

Especially in developing countries where compliance and follow up is the issue,

parenteral iron for treatment of iron deficiency anemia of moderate degree is useful.

10
In 1970, India was the first developing country to initiate nation wide a National Nutritional
Anemia Prophylaxis program, for prevention IDA in pregnant women.

Ministry of Health and Family Welfare in 2013 launched a program “National Iron Plus
Initiative” as a comprehensive strategy to combat the public health challenge of Iron Deficiency
Anaemia prevalent across the life cycle and more in pregnancy . There are age specific
interventions with Iron and Folic Acid Supplementation and Deworming for improving the
haemoglobin levels and reducing the prevalence of anaemia for all age groups including
pregnant women. (17)

Health campaign initiated by I-NIPI “Anemia mukt Bharat” with the objective of reduction of
anemia by POSHAN Abhiyaan launched in March 2018. In accordance with the targets of
POSHAN Abhiyaan and National Nutrition Strategy set by NITI Aayog, the Anemia Mukt Bharat
campaign has been designed to reduce prevalence of anemia by 3 percentage points per year
among children, adolescents and women in the reproductive age group (15–49 years), between
the year 2018 and 2022 .(18)

Anemia mukt bharat campaign operational guidelines recommend use of parenteral iron
sucrose for treatment of moderate and severe degree of anemia in pregnancy ..

In view of high prevalence of iron deficiency anemia and moreover inspite of multiple national
programs aimed at iron deficiency anemia with prophylactic oral iron supplementation in
pregnancy and recurrent failure to achieve target ,we need to find out the prevalence of iron
deficiency and better management options so,

This study aims on studying the prevalence of iron deficiency anemia in pregnancy and
comparision of response to treatment with parenteral iron and oral iron, to check if parenteral
iron significantly reduces the need of blood transfusion.

11
 AIM AND OBJECTIVES

1.) To study the prevalence of Iron Deficiency anemia in pregnancy by ruling out
hemoglobinopathies.
2.) To determine the prevalence of iron deficiency anemia on basis of age , gestational age
and gravida status .
3.) To determine the side effects of oral and parenteral iron.
4.) To study the response to the treatment to iron deficiency anemia in pregnancy with
parenteral iron compared to oral iron.
5.) To determine if parenteral iron treatment reduces the need of the blood transfusion in
pregnancy.

RESEARCH QUESTIONS

1.) To determine the prevalence of Iron Deficiency Anemia (IDA) in pregnancy and
2.) Comparison of response to the treatment with Oral and Parenteral iron.
3.) To check whether Parenteral iron treatment significantly reduces the number of BT in
pregnancy

HYPOTHESIS

1.) Response to treatment with parenteral iron is better than oral iron

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 REVIEW OF LITERATURE

Historical aspects:

Father of modern medical science and the great Greek philosopher Hippocrates (460-377 BC)
had said nearly 2500 years ago "Let thy food be thy medicine and thy medicine be thy food".
Our body has the inbuilt ability to heal itself if provided proper nutrition (19).

“…all these requisites belong of old to Medicine, and an origin and way have been found out,
by which many and elegant discoveries have been made, during a length of time,
and others will yet be found out, if a person possessed of the proper ability,
and knowing those discoveries which have been made,
should proceed from them to prosecute his investigations…”
(Hippocrates, On Ancient Medicine)

The word "anemia" is formed of two Greek roots which means "without blood" an (without)+
Haima (blood)(20).

Anemia was initially recognized as chlorosis (a Greek word which means green) "the green
sickness". Historians are yet to know, when this was first identified and appeared, but in the
16th century it was found that it is associated with symptoms and signs like i.e., fatigue, poor
appetite, palor, lethargy, neurological ,gastrointestinal and menstrual abnormalities commonly
seen in adolescent girls.

In Dutch school of painters, The pale hues of fatigued and fainting women were commonly
portrayed and were also referred to in several Shakespear's plays as love sick women.

Ancient Greek people knew the advantages of iron. The injured warriors during war use to
drink water in which the swords rusted.

Swammerdam in 1658 discovered red cells by looking the blood under microscope and called
them "ruddy globules" (21)

French Physician Gabriel II Andral gave the term anemia 1829 for chlorosis (22)

13
Sushruta described anemia as a form of ‘pandu roga ‘ or jaundice, believed it to be due to
derangement of kapha or phlegma and was manifested by whiteness of the eyes ,skin and
finger nails.

Charakha described form of pandu roga which is is asscociated with eating of clay , he treated
anemia with ‘rusted iron’ pills .

The condition known as Pica was described first by Hippocrates. (23) The term pica originates
in the Latin word for magpie (Picave), meanind eating disorder associated with iron deficiency
anemia. (24).

Before the twentieth century, most studies in the biochemistry of iron seemed to parallel, Lusk
(1917) commented that American families consumed 7 and 35 mg of iron daily, he implied
that, if this much amount was consumed, it was sufficient for normal functions

Bunge in 1902 stated ‘that consumption of foods poor in iron on daily basis may lead to
anaemia, but he contradicts this by saying ‘it is difficult that any diet would not contain the
small amounts of the metal required. Despite his statement regarding dietary iron deficiency
was almost unimaginable, Bunge considered that no food was rich enough in iron to be an
effective treatment for deficiency (Bunge, 1902). (25).

French physician Pierre. Blaud (1832) prescribed pills containing ferrous sulfate and potassium
carbonate for the treatment of anemia called as blaud’s pills (26)(27)

In 17th century Sydenham recommended ,that the anemia be treated with iron supplements
despite his statements chlorosis was classified among the hysterical diseases. (28)

Ralph Stockman in 1895 said that cause of chlorosis was nutritional iron deficiency, But this
view was ignored for decades before cause of anemia was established as nutrition in
twentieth century again (29)

By the end of the 19th century again , the incidence of chlorosis started increasing . It had
become an important topic of study of medical literature, but the true nature of the disease
remained understudied .

14
“Gold is for the mistress, Silver for the maid Copper for the Craftsman cunning at his trade
"Good" said the Baron, sitting in the hall, "But, Iron - Cold Iron, is master of them all". - Rudyard
Kipling (30)

The ferric hydroxide preparation , first iron compound for parenteral use introduced in early
decades of 20th century. Side effects of this preparation like no carbohydrate shell on this
compound caused immediate release of iron and resulted in severe fatal reactions, which
reduced its popularity and use only in extreme situations . Iron sucrose's first known use was in
Europe in 1949, it was used in US November 2000. It has replaced iron dextran, which was
used in US since the 1900s for treatment of iron deficiency (31).

The first high-molecular-weight iron dextran [HMW-ID]) for intramuscular and intravenous use
was introduced in 1954. (32)

DEFINITION:

According to WHO,

Anemia is a condition in which the number of red blood cells or their oxygen carrying capacity is
insufficient to meet the physiologic needs , which vary by age ,sex,altitude ,smoking and
pregnancy status .

Nutritional anemia was defined in a 1968 WHO technical report as:

“A condition in which the hemoglobin content of the blood is lower than normal as a result of a
deficiency of one or more essential nutrients, regardless of the cause of such deficiency.” (33)

The definition of anemia recommended by the Centre for Disease Control and Prevention is a
haemoglobin or hemotacrit value less than the fifth percentile of the distribution of Hgb or Hct
in a healthy reference population based on the stage of pregnancy .(34)

15
According to Robins pathology, anemia is a hematological disorder characterized by reduction
in circulating red cell mass and corresponding decrease in hemoglobin mass and oxygen
carrying capacity.

Anemia is a decrease in the total amount of red blood cells (RBCs) or hemoglobin in the blood
or a lowered ability of the blood to carry oxygen (35).

In pregnancy,

Iron deficiency anemia is defined as hemoglobin of less than 11g% in the first and third
trimester of pregnancy and less than 10.5g% in the second trimester of pregnancy
(36)(37)(38)(39)(40).

According to UK guidelines , Anemia is defined by hemoglobin of less than 110gms/l in first

trimester, 105gms/l in second and third trimester and 100gms/l in postpartum period(41).

Degree of anemia :

WHO (2002), classification of anemia into three categories, depending on hemoglobin levels.

TABLE A

SEVERITY HEMOGLOBIN

1 Mild 9.1-11 gm/dl

2 Moderate 7.1 -9gm/dl

3 Severe <7gm/dl

16
Indian council of medical research (1989) classifies anemia as :

TABLE B

Category severity Hemoglobin level(gm/dl)

1 mild 10-10.9

2 moderate 7-9.9

3 severe 4-6-9

4. Very severe (decompensated) <4

WHO (2000) classification of anemia , (42)

Hemoglobin percentage is represented in gm/l instead of gm/dl.

TABLE C

Severity of anemia Hemoglobin(g/lit) Erythrocyte volume fraction

Mild * 100-109 0.30-0.32

moderate 70-99 0.21-0.29

severe <70 <0.21

*mild is misnomer, iron deficiency is already advanced by the time anemia is detected.

The deficiency has functional consequences even if anemia is not clinically apparent.

WHO(2011) cutoff value in pregnancy,

17
TABLE D

Pregnancy state Normal(Hb/dl) Mild(hb/dl/) Moderate(hb/dl) Severe(hb/dl)

1st trimester 11 10-10.9 7-9.9 <7

2nd trimester 10.5 - - <7

3rd trimester 11 10-10.9 7-9.9 <7

According to British committee on standards of hematology, 2011 (43)

TABLE E

Serial no. Pregnancy trimester Hemoglobin (gm/l)

1 1st trimester <110gms/l

2 2nd trimester <105gm/l

3 3rd trimester <105gms/l

4 Post partum <100gms/l

Altitude above sea level and smoking modify Hb concentration (44). The ever rising mother’s
blood volume and iron requirements accounts for the dramatic change in Hb concentration in
a normal healthy woman. The Hb concentrations start to decrease in the first trimester and
continues to decline and reach minimum in the second trimester, and start to increase again in
the third trimester. Currently, the Hb cut-off according to pregnancy trimester has not been
defined by WHO, a value of -1.0 g/dL is suggested suggested for unknown trimester.
Nonetheless, Nestel P has developed a table for adjustment of hemoglobin for all trimesters ,

18
Hemoglobin concentration is the commonest hematological estimation and there is a strong
correlation between Hb concentration and serum ferritin levels (45)

Hemoglobin adjustment for pregnant women living at sea level (46)

TABLE F

Serial no. trimester Hemoglobin (hb/dl) adjustments

1 1st trimester -1.0

2 2nd trimester -1.5

3 3rd trimester -1.0

4 unknown -1.0

Absolute iron deficiency is serum ferritin <15mcg/l regardless of whether anemia is present .

Iron deficiency anemia is serum ferritin <15mcg and hemoglobin fulfill the definition of anemia.

Latent iron deficiency is serum ferritin <15 mcg/l but hemoglobin levels are within the non
anemic range.

Functional iron defieciency is serum ferritin is normal or even elevated, but transferrin
saturation is reduced or hypochromic erythrocyte fraction <10%.

Incidence and prevalence:

Anemia is global issue, nutritional anemia is the most common cause of anemia worldwide and
in India too.

For the year 2011 global prevalence of anemia (WHO) states that 38% of pregnant women, of
32 million population is suffering from anemia. s. In 2011, the WHO South-East Asia along with
Eastern Mediterranean and African Regions had the lowest mean blood haemoglobin

19
concentrations and the highest prevalence of anaemia. The prevalence of anaemia was 38.9%
to 48.7% for pregnant women in these regions. Decreasing the prevalence of anaemia is
recognized as an important part of the health of women and children, and the second global
nutrition target for 2025 calls for a 50% reduction of anaemia in women of reproductive age .In
India mean hemoglobin concentration is 108 amongst pregnant women (47).

“World Health Organization (WHO)/World Health Statistics data shows that 40.1% of pregnant
women worldwide were anemic in 2016. “ as per NHP.

In India as per national family health survey (NHFS-4) 2015-2016 prevalence is 58% in pregnant
women .,it has reduced by 8% from year 2005-2006 survey NHFS-3 .

I. IMAGE

TABLE G. National family health survey -4 (2015-16)

>40 % Maharashtra, Rajasthan, Gujrat, Madhya Pradesh, Punjab, west Bengal ,Bihar,
Uttar Pradesh ,Haryana,

20-39.9% Jammu Kashmir and few eastern states,kerala

5-19.9% -

<5% -

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II. IMAGE

In India, estimated maternal deaths due to IDA is approximately 3,26,000 with an associated
disability-adjusted life years (DALYs) of 12,497,000 (48).

Classification of anemia in pregnancy:

1 .Physiological anemia of pregnancy.

2. Pathological :

A. nutritional anemia

a. iron deficiency

b. folate deficiency

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 c. vitamin b12 deficiency

B. hemorrhage

a. acute early trimester bleeding ,APH.

b. chronic anemia: hookworm and other parasitic infestations .

C. hemolytic anemias:

a. congenital:

- G6pd deficiency

-hereditary spherocytosis.

b. acquired:

-Microangiopathic hemolytic anemia

-Acquired immune-hemolytic anemia

D . hemoglobinopathies

a. Sickle cell disease

b. Thalassemia

c .Aplastic anemia

Causes Of Iron Deficiency Anemia In Pregnancy:

I. Dietary factors:
a. low dietary intake, poor iron (less than 20 mg /day) and folic acid intake (less than 70
mg/day) consumption.(49)

b. low absorption of iron :poor bioavailability of iron (3-4% only) in phytate and fibre-rich
Indian diet. Consumption of iron tablets with calcium ,tea , herbal tea .

22
 c. certain food taboos , faulty washing techniques of green leafy vegetables.

II. Increased demand during pregnancy :

The iron requirement during pregnancy significantly increases despite the temporary relief
from iron losses of menstruation. Iron requirements decrease during the first trimester
because menstruation stops, which represents a median saving of 0.56 mg Fe/d (160
mg/pregnancy) (50).hemodynamic changes occurring early in pregnancy are generalized
vasodilation, increase in the plasma volume, and an increase in red blood cell 2,3-
diphosphoglycerate concentrations (51).

Iron requirements increases during the second half of pregnancy because of the great
expansion of the red blood cell volume and the transfer to growing fetus and the placental
structures., uterus .

From the second trimester, iron requirements begin to increase and continue to do so
throughout the pregnancy. There is increase in oxygen consumption by both mother and
fetus .” Most studies in women supplemented with iron show a change in total blood
volume of ≈45%, with an increase in plasma volume of ≈50% and an increase in red blood
cell mass of ≈35% , The rise in hemoglobin mass is similar at ≈30%” (52)
As pregnancy advances , iron requirements for growth of fetus steadily increases in
proportion to the fetal weight, and most of the iron accumulates during the third
trimester.

23
TABLE H- Iron requirements in pregnancy(53)

Total cost of pregnancy mg

Fetus 270

Placenta 90

Expansion of red blood cell mass 450

Obligatory basal losses 230

Sum 1040

Maternal blood loss at delivery 150

Total cost 1190

Net cost of pregnancy

Contraction of maternal red blood cell mass −450

Absence of menstruation during pregnancy −160

Subtotal −610

Net cost 580

C .Maternal causes

Many Indian women enter pregnancy with depleted iron stores.

Frequent repeated pregnancy –grand multipara associated with preeclampsia , APH,PPH

Short intervals in pregnancy ,less stores of iron as utIlised in earlier pregnancy and less time foe
storage of iron in next pregnancy

Multiple pregnancies

24
Chronic illnesses.

D .Socio cultural factors:

Poor socioeconomic status: poor nutrition ,large family size

illiteracy

Cultural belief, cooking and eating habbits

food taboos ,like pregnant women avoid meat ,fish ,egg ,jaggery, curds ,milk ,leafy vegetable,

over cooking of food ,washing of vegetables.

E. infection and infestation: (54)

a. Hookworm infestation one of the causes of nutritional anemia among pregnant

women. The worms – whipworm ,roundworm, hookworm either cause anemia or
aggravate the preexisting one. Hookworm also leads to folic acid deficiency in pregnant
woman.

b.malaria –plasmodium falciparum cause profound anemia if occurs during pregnancy.

Clinical features of anemia: (55)

symptoms:

sometimes anemia presents with no symptoms till it progresses the severe anemia,
common symptoms like weakness, or is often masked by symptoms of pregnancy,
exhaustion and lassitude ,indigestion, loss of appetite ,palpitation, giddiness
,dyspnoea, orthopnea, edema ,rare cases anasarca , chronic cardiac failure in severe
cases, loss of hair , mouth ulcers ,

25
 signs:

Pallor.

tachycardia

glossitis (reddened , swollen ,smooth, shiny ,tender tongue),angular stomatitis,

koilonychias (spoon shaped nails)

platynychia (thin ,lusterless ,brittle, flattened nails)

edema on feet

soft systolic murmur on auscultation

raised respiratory rate in severe cases

basal crepitations (CCF).

Signs related to pregnancy:

On per abdominal examination:

Fundal height less than period of amenorrhoea often due to IUGR, oligohydramnios .

Signs related to associated illnesses :

Blood in stools

Hematuria

Low urine output

High grade fever with chills.

Complications of anemia in pregnancy:

1. During pregnancy

1st trimester:

26
 IUGR , low birth weight, depressed immune system ,recurrent infections, flare up of old
lesions

mid trimester:

preterm birth, PPROM , in severe anemias –heart failure at 30-32 weeks, APH ,
preeclampsia aggravates placental abruption ,IUFD

2. During labour

Maternal death

Still birth

PPH is real threat

Due to IUGR and multiparity most of the times labor is short

cardiac failure immediately post delivery , autotransfusion – increased load on weak

heart already compromised by hypoxia.

shock – minor traumatic delivery w/o bleeding may produce shock or hypoxia during
anesthesia can also cause shock

3. Puerperium

puerperal sepsis subinvolution of uterus

failure of lactation, puerperal venous thrombosis

pulmonary embolism

Deep venous thrombosis

4. Risk Periods

30-32weeks as demand is significantly high during thia period ,during labour

27
 Immediately following delivery

Anytime in puerperium sp. 7-10 days following delivery – pulmonary embolism

5. Effects On Fetus

Incidence of low birth weight increases 2- fold and perinatal mortality 2-3 fold when
maternal HB <8 g/dl.

No NICU admissions increase

Moderate anemia before 28 weeks associated with increase risk of still birth.

Impared psychomotor/mental development of the child

Negative impact on social and emotional behaviour .

Physiological changes in blood during pregnancy: (56)

In pregnancy, serum iron needs to increase in sufficient amount for fetoplacental growth and
development and adaptation of mother to pregnancy. To meet iron requirements, iron
absorption from diet and the utilization of iron stores increase, this mechanism in large part is
dependent on hepcidin, iron-regulatory hormone. Maternal hepcidin concentrations are
decrease in the second and third trimesters and facilitates supply of iron into the circulation in
a healthy mother. This mechanism of hepcidin suppression in pregnancy is unknown, but
hepcidin regulation by iron, erythropoietic activity, and inflammation is functional during
pregnancy. Increased hepcidin in mother during pregnancy can reduce the availability of iron
for transfer to placenta and also impair the efficacy of supplementation of iron. The fetal
hepcidin role in the regulation of placental iron transfer still under study.

Iron requirement in pregnancy as discussed in table: above.

Regulation of iron availability :

In asseessment the uptake of stable or radioactive iron isotopes, shows increased absorption
of nonheme iron during pregnancy as gestation progresses (57) and heme absorption also

28
increases in a similar manner .During pregnancy, liver and spleen iron contents are less as
shown in studies in animal models compared with non pregnancy concentrations that means
iron is mobilized .thus there is increase in iron availability for transfer through the placenta to
fetus and for mother’s hematologic adaptation.

The regulation of iron availability during pregnancy is to some extent dependent on maternal se
hepcidin levels. Hepcidin,is an iron-regulatory hormone, is produced in the liver , regulates
level of plasma iron and distribution of iron in tissue (58). It inhibits major iron concentration
into plasma through , iron absorption from intestines and mobilization of stored iron from the
liver (Figure- ). Hepcidin receptor is iron exporter ferroportin. Ferroportin is present in all the
tissues that transfer iron into plasma . Hepcidin after binding to ferroportin triggers its
degradation and results in sequestration of iron in target cells and decreased iron flow into
plasma. Thus, iron delivery to consuming tissues, example fetus is inversely correlated with
hepcidin concentra

Few studies have states during healthy pregnancy, maternal hepcidin concentrations are
decreased in the second and third trimesters in humans (59) thus increasing circulation of iron .

In a study conducted in 19 pregnant women who were given stable iron isotopes during third
trimesters showed that thedietary heme and non heme iron that was transferred to the fetus
was inversely correlated with maternal serum hepcidin measured during delivery (60). The
mechanism of suppression of maternal hepcidin during pregnancy is not known.

1. Plasma dilution can partially contribute, but tne moagnitude with which it drops cannot be
explained by plasma volume and plasma dilution cannot explain the suppression of hepatic
hepcidin messenger RNA that has been observed in animal studies .
2. The gradual development of ID may also be a signal to suppress hepcidin.
3. Iron , erythropoietic activity (suppresses hepcidin).

Effect of Iron supplementation on maternal hepcidin during pregnancy is not known. Iron
supplements in nonpregnant adults increases hepcidin rapidly (61) and, decreases iron

29
absorption. If iron supplementation in pregnancy has the same effect on maternal hepcidin,
daily iron supplementation may not be optimal to achieve the most efficient iron absorption.

“A 2015 Cochrane review from 15 countries, randomized trial showed that maternal and
infant outcomes at birth were not better with daily iron supplementation compared with
intermittent iron supplementation, but intermittent supplementation was associated with
fewer side effects “(56).

Fetal hepcidin in regulating placental iron transfer:

During pregnancy, fetal hepcidin could also determine the rate of placental iron transfer . here,
maternal hepcidin would regulate the amount of iron that goes to the placenta for utilisation,
on the part fetal hepcidin regulates, the transport of iron into the fetal circulation from
placenta.

Hematologic variables :

blood volume: hypervolumia 40-45%, begins to rise by 1st trimester ,15% by 12weeks,

rapid increase by 2nd trimester , slower by 3rd trimester and plateau.

Reasons:

1. Meet the metabolic needs of enlarged uterus and greatly hypertrophied vascular
system.

2. Provide abundant nutrients and elements to support rapidly growing placenta and
fetus.

3. Protects mother and fetus against deleterious effects of impared venous return in
supine position and erect position.

4. Safeguard mother against adverse effects of parturation associated blood loss.

Erythrocytes:450 ml of rise.

Moderate erythroid hyperplasia in bone marrow

30
 Reticulocyte count – increases slightly

Erythropoitin –increases

Hemoglobin concentration and hematocrit : hb decreases ,

hematocrit-decreases,

whole blood viscosity –decreases.

hemoglobin <11gms/dl is abnormal d/t iron deficiency and due to hypervolumia.

iron metabolism-

storage iron- total iron content –adult female- 2-2.5 gms.

normal iron stores are 300mg .

most iron is used during the later half of pregnancy , iron requirement increases in 2nd
trimester to 6-7mg/day

In most women it is not available as iron stores,thus hb and hct fall appreciably as
plasma volume increases ,at the same time fetal hb levels are not affected as fetus uses
iron from maternal store and has high affinity to oxygen, thus fetus can with stand
severe maternal anemia also.

If supplemental iron are not given to normal pregnant women , serum iron and ferritin
conc. falls in midpregnancy.

Early increases in se iron and ferritin are likely d/t minimal early iron demand combined

with positive iron balance from amenorrhoea.

Changes in iron variables during pregnancy:

The Serum ferritin concentration is the most commonly used marker for determination of iron
stores. Ferritin is secreted by macrophages and, by hepatocytes in less amount , intracellular
iron. Because ferritin production is controlled by inflammatory cytokines also, Serum Ferritin

31
may not accurately show iron stores in the presence of inflammation. Se Ferritin level gradually
decrease to lowest in the third trimester.

Serum iron and TSAT decreases during pregnancy but to lesser degrees in pregnancies
supplemented with iron (62) The plasma iron compartment is small in comparision with iron
stores and has diurnal variation and can alter very quickly after iron ingestion etc. this is why,
serum iron and TSAT are inferior to Se Ferritin for diagnosis of iron Deficiency .

In pregnancy, sTfR concentrations do not change much compared with nonpregnant status
unless maternal erythropoiesis is iron deficient (63). Thus, sTfR concentration mays only mildly
increase by the third trimester but increase substantially in women with Iron deficiency anemia
Because sTfR is not altered by inflammatory response , it is a better marker of iron-deficiency
than serum ferritin in the presence of inflammation.

The table I, below shows impact of pregnancy on following parameters(64)

32
Table I : IMPACT OF PREGNANCY ON HEMATOLOGICAL PARAMETERS AND CARDIAC SYSTEM

PARAMETERS INCREASE DECREASE REMARKS

CARDIAC OUTPUT INCREASES 40%

STROKE VOLUME INCREASES

PLASMA VOLUME INCREASES 50%

RED CELL MASS INCREASES 25%

HEMOGLOBIN DECREASES DECREASES MORE IN 2ND TRIMESTER

HEMATOCRIT DECREASES DECREASES MORE IN 2ND TRIMESTER

MCV INCREASES MINIMALLY

MCHC - UNCHANGED THROUGH OUT

IRON REQUIREMENT INCREASES 2-3TIMES

SE IRON DECREASES

SE FERRITIN DECREASES

WBC INCREASES

LYMPHOCYTES AND MONOCYTES UNCHANGED

PLATELETS DECREASES 15%

FACTOR 5,7,10,12 AND VON WILLEBRAND INCREASES HYPERCOAGULABLE

STATE

FIBRINOGEN ,FACTOR 8 INCREASES SIGNIFICANTLY

ANTITHROMBIN 3 AND PROTEIN C UNCHANGED

PROTEIN S AND PLASMINOGEN ACTIVATOR DECREASES BY 40%

INHIBITOR
Placental iron transport:
During pregnancy, the placenta keeps ∼90 mg iron for use , and sends average 270 mg iron to
the fetus. Most of the iron transfer occurs in third trimester , The transport of nonheme iron
through placenta to the fetus is one way only.(65), and this transfer coincides with the low
hepcidin concentration in mother serum, which gives maximum iron supply to maternal
circulation. Maternal transferrin production steadily increases during pregnancy which may
function to increase iron delivery to the placenta.

Placental iron transport. On the apical side of the syncytiotrophoblast, maternal iron Tf binds to
TfR1. After internalization, iron dissociates from Tf, and is reduced by a ferrireductase, and is
exported from the endosome into the cytoplasm, via DMT1 or another transporter. Iron is
exported from the syncytiotrophoblast by Fpn and oxidized by a ferroxidase and loaded on fetal
Tf or is transferred into fetal circulation but mechanism of Iron transport across the fetal
endothelium is yet unsolved.

Iron requirement in pregnancy:

According to food and nutrition board of medicine ,2008 (66)

Recommended daily dietary allowances for adolescent and adult pregnant and lactating
women :

34
Iron requirement in pregnancy (14-50 years)- 27mgsof which 15% is absorbed

Iron requirement in lactating women -10mgs (14-18yrs) and 9 mgs(19-50yrs)

Factors affecting iron absorption :

Iron absorption :The balance of iron is regulated solely by gastrointestinal system –

proximal small intestines –iron taken up by brush border of luminal cells- facilitated by
acidic contents of stomach.

Iron transport: Ferrous iron is transported into enterocyte by apical membrane iron
transporter called divalent metal transporter ( DMT1), some iron stored as ferritin and
some transported out by basolateral tranporter ferroportin 1 from enterocytes.

In plasma ferrous iron is converted to ferric iron and binds to transferrin . Heme is
transported into the enterocyte by heme transporter , ferrous form is released from
heme by heme oxidase and converted to ferric and binds to ferritin. The rest of iron
binds to basolateral ferrous transporter ferroportin (FP),binds to transferrin and is
stored in the body as ferritin and hemosiderin .

Cells containing ferritin are exfoliated from mucosal surfaces every 2-3 days.

Transferrin does not cross placenta, but transports its iron through chorionic villus,iron
transport is enzyme dependent.

Factors decrease iron absorption :

phytates ,calcium ,tannins, tea and coffee, herbal drinks .

Factors increase iron absorption:

Hydrochloric acid –favours dissolution and reduction of ferric iron to ferrous iron

reducing substances like ascorbic acid , aminoacids

meat has organic iron and increases HCL secretion

35
 low phosphorus diet.

Iron deficiency anemia:

Pathophysiology and stages of iron deficiency anemia

Increased demand in pregnancy

Increased absorption from intestine

Mobilisation of iron stores

If inadequate intake , reduced absorption or

bleeding

Iron stores are depleted STAGE 1 (LOW FERRITIN )

Serum ferritin level fall and transferrin saturation decreases

Decreased supply of iron to erythroid precursor

Iron restricted erythropoiesis STAGE 2 (INCREASE IN ERYTHROCYTE

PROTOPORPHYRIN

Accumulation of free erythrocyte protoporphyrin

36

Reduced erythrocyte indices STAGE 3 ( LOW HB , MCV, MCH, MCHC)

 TABLE J - Stages of development of iron deficiency anemia : (67)

Normal Iron depletion Iron deficient IDA

erythropoiesis

MCV (fl/cell) 80-100 ↓ ↓ ↓

RDW-CV (%) 11.5-14.5 ↑ ↑ ↑

STfR (MG/L) 1.8-4.6 ↑ ↑ ↑

Plasma ferritin 100+/- 60 <20 10 <10

(mcg/L)

TfR:SF ratio > 0.975 ↑ ↑ ↑

TIBC(ug/) 330+/-30 360 390 410

Transferrin 35+/-15 30 <15 <10

saturation(%)

Plasma iron 115+/-50 115 <60 <40

(mcg/dl)

ZPP (mcg/dl) <60 <60 60-80 >80

Iron absorption 5-10 10-15 10-20 10-20

(%)

Sideroblasts (%) 40-60 40-60 <10 <10

00 37
 Hematocrit(%) 33 33 <33 <32

Hemoglobin( >11 >11 >11 <11

g/dl)

Table represents the progressive changes in test values during the three stages of iron
deficiency anemia

Diagnosis: Diagnosis of iron deficiency anemia is very challenging , along with proper history
,important is doing appropriate investigation for labeling the disease as iron deficiency anemia

Assessment of iron deficiency anemia can be done by four groups of tests ,refer K table below.

TABLE K . ASSESSMENT OF IDA

Serial Group of investigation Parameters assessed

no.

1 Red blood cells parameters and Hemoglobin, MCV, MCH, MCHC ,RDW,
indices reticulocyte count,peripheral smear.

2. Direct measurement of iron stores Se. iron, total iron binding capacity, percent
saturation, se. ferritin, bone marrow biopsy

3. Assessment of heme iron Free erythrocyte protoporphyrin

4. Iron intake assessment Soluble transferrin receptor (sTfR), soluble

transferrin receptor-log [ferritin] (sTfR-F) index,
zinc protoporphyrin(ZPP).

1.Red blood cells parameters and indices: first step for diagnosis of IDA is complete
blood count(CBC) - Hb, MCV, MCH, and MCHC (68)(69).It is easy , cheap, rapidly
performed and predictd early IDA.

00 38
  Blood smear could provide important information in the diagnosis of anemias.
Peripheral blood smear help in differentiating the IDA from megaloblastic anemia,
chronic anemias . Oval shaped macrocytes and hyper segmented neutrophils are
associated with megaloblastic anemias ,target cells and pencil cells are seen in IDA
(70) and they rule out anemia of chronic diseases . Poikilocytes are also observed
in more numbers in IDA (71).
 Low Hb and reduced MCV is usually the first finding on a routine CBC. The severity of
anemia is based on the patient’s Hb/hematocrit level.
 Mean corpuscular volume -average RBC volume,
 MCHC - the measure concentration of Hb in a given volume of packed RBCs
 Red cell distribution width has a better sensitivity than MCV for the diagnosis of IDA
(72). The RDW is a measure of the change in RBC width and along with MCV it
distinguishes anemia of multiple cause. After treatment ,there is profound
reticulocytosis in first 4 weeks and seen as a sudden increase in RDW, sometimes to
over 30% (73)
 Falling MCV and rising RDW should alert the clinician for possible IDA and then confirm
by marked RDW increase occurring early after the initiation of therapy .
 A few studies have reported sensitivity and specificity, respectively, of RDW in the
diagnosis of IDA in pregnancy; Sultana et al, 97.4% and 83.2%; and Tiwari et al, 72.8%
and 82.4%
 Microcytosis is observed in the peripheral smear even before CBC alters. The
presence of microcytic hypochromic red cells and “photo pencil cells” are indicative of
IDA .
 Often platelet count are greater than 450,000/µL in IDA, and the red cell count falls.
 Iron deficiency anemia is characterized by microcytic RBCs. Other conditions
causing microcytic RBCs include anemia of chronic disorders, βthalassemia, and
sideroblastic anemia.
 differential diagnosis of various microcytic anemias (74), below table -L

00 39
 TABLE L - DIFFERENTIAL DIAGNOSIS OF VARIOUS MICROCYTIC ANEMIAS

Indicator Iron deficiency b-thalassemia Sideroblastic Acute chronic

anemia anemia inflammation
hemoglobin decreased Normal/decreased - decreased

ferritin decreased Normal/increased Normal/increased Normal/increased

Serum iron decreased Normal/ increased Normal/increased Normal/decreased

TIBC increased Normal Normal decreased

TS decreased Normal to Normal Normal

increased /increased /decreased
sTfR Increased in More 100mg/l - normal
severe IDA
FEP increased normal - increased

MCV decreased decreased normal Normal or

decreased
RDW increased Normal to increased Normal
increased
reticulocytes decreased - - Normal or
decreased
Mentzer index Increased (>13) Decreased (<13) - -

 Mentzer index (MCV/RBC count) is the most reliable index with high sensitivity
(75) Mentzer Index>13indicates IDA and < 13 indicates thalassemia.

00 40
  wo studies from Middle-East have reported RBC count as above 5 × 10 6 /mm 3 inβ-
thalassemia subjects whereas in IDA patients it is below that value (76) (77).

2. Serum ferritin :

Serum ferritin Ferritin is a sensitive indicator of IDA in pregnant women(78).

 Serum ferritin is acute phase reactant, it reflects ID in the absence of inflammation

 serum concentration below15 μg/L indicates iron depletion in all stages .
 However, treatment needs to be initiated when the concentration falls below
30μg/L, as this indicates early iron depletion.

3. Soluble transferrin receptor (sTFR):

 It is a sensitive measure of iron supply , it is an expensive test.
 It is a transmembrane protein which transports circulating iron into the RBCs and
is expressed on erythrocyte membranes;sTfR and total transferrin
concentrations are directly proportional.(79)
 There is steady increase in mean sTfR concentration as pregnancy advances.
 The increase is influenced by high erythropoietic activity than by iron
depletion(80).

4. Serum Iron, and total iron binding capacity (TIBC): (81)

 Serum iron and TIBC are the other independent indicators of marks iron store.
 The TIBC measures the obtainability of iron-binding sites.
 . The TIBC decreases with malnutrition, inflammation, chronic infection, and
cancer.

5. Erythrocyte Zinc Protoporphyrin (EPP) and Zinc protoporphyrin (ZPP):

00 41
  Shortage of supply of iron in IDA increases ZPP production and e ZPP/heme
ratio increases, whereas in normal condition the reaction of ZPP with iron
predominates
 This test is reported as the ZPP or ZPP/heme ratio.
 It is a sensitive but not specific, as ZPP increases in inflammation, lead
poisoning, anemia in chronic disease, and hemoglobinopathies .
 Normal value of ZPP< 2.3 micrograms ZPP/g Hb (82).
6. Reticulocyte hemoglobin content :
 Reticulocyte Hb concentration indicates ,amount of iron presented to the bone
marrow for uptake into new RBCs.
 This test is not routinely available.
 The sensitivity and specificity of this test is like se ferritin.
7. Bone Marrow biopsy :
 Bone marrow biopsy is considered to make a definitive diagnosis of IDA ,when
the diagnosis is uncertain after the laboratory results.
 It is indicated when there is no response to treatment or to rule out other
conditions.
 The absence of stainable iron is the ‘gold standard’ for diagnosis of IDA.
8. Trial of iron therapy: (83)
An increase of at least 1 g/dL in hemoglobin or 0.03 l/l in hematocrit after 1 or 2 months
of supplementation shows an adequate response to treatment and confirms the
diagnosis of IDA .
9. Urine routine and microscopy:
10. Stool routine and mcroscopy:
11. If clinical scenario demands :
 Sputum examination
 RFT in suspected CKD pts
 Serum protein in hypoproteinemia

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 Management

 Preconceptional counselling : plays a very important role in prevention of iron

deficiency anemia according to ministry of family welfare
• Intensify awareness

• As maximum no . of pts in india entering pregnancy are iron deficient and hence the
prevalance in pregnancy is high .

• Preconception CBC should be advised and managed .

• Correction of the same to achieve target of 11gms/dl with proper dietary advise and
treatment.

• Screening for non nutritional anemias in endemic areas .

Pts not responding to treatment –refer to higher centre for diagnosis and management

• Correct underlying cause

• Appropriate diagnosis of congenital anemia .

• Serum B12 levels should be assessed

• Start folic acid 5mg daily before conception .

• Deworming should be considered.

• Dietary modification.

 Oral iron prophylaxis :

The policy of oral iron prophylaxis varies in different countries.

00 43
 TABLE M . Recommendations of various programs: (84)(85)(86)

Serial program Recommendations Recommendations remarks

no.
prophylaxis Treatment

1 World health organization Daily 60 mg Daily 120 mg

iron+400 µg folic iron+400 µg folic Prevalence
acid till term acid till term >40% then
additional
3months

2 Ministry of health and family Daily 100 mg Mild anemia- 2 IFA

welfare iron+500 µg folic tablets/day-100 days
acid- for 100 days  Moderate anemia-
starting after IM iron therapy+oral
thefirst trimester, folic acid
at 14-16 weeks of
gestation

3 1.national nutritional 100mg of Double the dose

anemia control programme elemental iron plus
of india,1999 500mcg of folic acid
for for minimum of
2.national consultation on
100 days starting
control of nutrtional anemia
from 2nd trimester.
in india,1997.

3.child survival and safe

motherhood programme,
1991 recommends

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 4. American college of recommends
obstetrics and gynaecology 30mgs elemental
iron/day 60-
100mgs in larger
women, multiple
gestation

Different types of iron preparation :

Ferrous Sulphate-300 Mg =60mgs Elemental Iron

Ferrous Gluconate-500mg =60mgs Elemental Iron

Ferrous Fumarate-180mg=60mgs Of Elemenatal Iron

Ferrous Calcium Citrate Citrate -556mgs=50mgs

Ferrous Succinate- 100mg=35mgs

Sustained Release (Ferrous Sulphate)- 350mgs=105mg

Ferrous Ascorbate -100mg Of Elemental Iron

Various iron salts commonly used for the treatment of anemia in India.

A systematic review, which included about 10,695 patients, found extended-release ferrous
sulphate with mucoproteose to be the most tolerated oral iron supplement of the various
formulations evaluated (87)

In an RCT, comparing various iron supplements in pregnant women, ferrous ascorbate and
bisglycinate were more effective and better tolerated than ferrous sulphate(88)

00 45
 The GI side effects are associated with poor compliance to iron supplementation in pregnant
women in India (89). A subgroup analysis from 7 RCTs in a systematic review has demonstrated
a statistically significant increased risk of GI side effects with ferrous sulphate in pregnant
women (n=1028). These side effects include diarrhea, constipation, abdominal pain, flatulence,
nausea, black or tarry stools and heartburn(90). Drug interactions are also a major concern of
oral iron pills as they interact with many drugs (91).

Disadvantage of oral iron therapy:

Intolerance

Unpredicatable absorption

Replenishment of iron stores takes longer time

Poor compliance due to sideeffects .

 Parenteral iron therapy :

Indications : Drawback of oral iron Is poor compliance because of less tolerability and side
effects. The side effects of oral iron further precipitate the pregnancy associated
Gastrointestinal disturbances like indigestion, constipation, nausea, vomiting, and reflux
esophagitis .Hence, parenteral iron can be given in place of oral iron in patients who

cannot tolerate oral iron,

non-compliant

need of rapid restoration of iron stores.

Parenteral iron can be used in the pregnancy and during the postpartum period.

parenteral iron therapy – prerequisites:

confirm diagnosis of iron deficiency .

The infusion should be carried out only under supervision and in place where availability for
the management of anaphylaxis .

00 46
 Sensitivity test prior to infusion is recommended.

Contraindications to parenteral iron are

1. A history of anaphylactic reactions to parenteral iron therapy.

2. First trimester of pregnancy, chronic liver disease and active infection (acute or chronic).
No evidence on theuse of IV iron in the first trimester of pregnancy is present. ( 92,93).

3. Oral Iron should be stopped at least 24 hours prior to therapy to avoid toxic reaction (94).

Dose calculation:

 TOTAL DOSE (mg) = 2.4 × WEIGHT (KGS) × d + 500mg

- d = HB DEFICIT

HB DEFICIT =TARGET HB (11GM%)- ACTUAL HB .

- 0.24 IS CORRECTION FACTOR CONSIDERING PTS BLOOD VOLUME, (0.24*10)

For this Calculation the iron content of hemoglobin =0.34%

Blood volume =7% of body weight and,

1,000 is conversion from g to mg

So, 0.24=0.0034*0.07*1,000

- 500 MGs= IRON STORES ,WT>35KGS.

<35kgs=15mg/kg body wt .
- Use ideal body weigh in obese pts ,body weight is pre pregnancy

 250mgs*deficit hemoglobin%

 hemoglobin deficit (gm/dl)*weight (kg)*2.21+1000

00 47
 Different types of parenteral iron :

There are four different groups of parenteral iron preparation are available , classified
according to kinetic and thermodynamic factors.

They differ essentially In complex stability ,molecular mass, toxicity ,pharmacokinetics and
side effects.

Type 1 Type 2 Type 3 Type 4

Examples Iron dextran Iron sucrose Iron gluconate, Iron(III)-citrate +

iron(III)-sorbitol +
Iron dextrin Citrate and iron
iron dextrin
(3) sorbitol
Sodium ferric
gluconate + iron
sucrose

Iron sucrose:

Iron sucrose is commonly used preparation for IV infusion and is safe with fewer adverse
events in pregnancy. sucrose complex is transferred to bone marrow for erythropoiesis
and then excess into reticuloendothelial system for storage. (95)

Iron sucrose does not require to administer a test dose(96)

In various studies conducted , iv iron sucrose has proven to be more efficacious , safe , with
less effects and better response for rise in mean hemoglobin and hematocrit and iron
storage .

A study done to compare the efficacy of two and three doses of intravenous iron sucrose
with oral iron therapy, there was higher no. responders with hb >11gm% in intravenous
group (75 vs. 80%). Significant difference of iron stores before delivery (ferritin >50 mg/l)

00 48
 in the group with three intravenous iron doses in comparison to the oral iron group (49 vs.
14%; P<0.001)was noted.(97).

A study conducted to evaluate the safety and efficacy of iron sucrose in dialysis patients
who were sensitive to iron dextran, demonstrated the safety of iv iron sucrose injection.(98)

Numerous studies in India have evaluated the effectiveness of IV iron as a first line
treatment in moderate to severe anemia during second and third trimester of pregnancy.

After an observational study conducted in India ,in 2 states by MoHFW with WHO,
requirement of standard guidelines and protocols were formulated. (99)
It is FDA approved drug, category B.

Iron Sucrose (100)

A. Chemistry

Na2FeO8(OH)3(H2O)n.m(C12H22O11)

Intravenous iron sucrose is a sterile, aqueous, complex of polymer iron 3 hydroxide in

sucrose, molecular wt. is <60,000daltons,ph 10.5-11.1

Mechanism of action : Following intravenous administration, It is dissociated in iron and

sucrose by RE system .Iron is transferred to liver and bone marrow . Ferritin
sequestration

in a non ionic form from which iron is easily available.

Pharmacokinetics:

1st order kinetics

Elimination : 6hrs

Total clearance : 1.2/lit

Peak iron levels of 538µmol/l (30mg/l) in 10 mins after injection .

00 49
 Bioavailability: High level of radioactivity within 5mins , in liver and bone marrow is
indicative of high concentration of iron reaching bone marrow

Elimination: maximum is excreted mainly by urinary excretion in 4hrs

B.Availability:

2.5ml and 5ml single dose amp containing 50mgand 100mg elemental iron.

C. Safety profile: (101) (102)

Rare,minor side effects

Allergic reactions3.3cases/million/year

D. Dosage calculation: described earlier

E.Administration:

Iv,2.5ml diluted in a maximum of 100ml of 0.9%nacl,immediately prior to infusion and

infuse over 30mins .

Unused diluted solution must be discarded.

Maximum dose:max of 200mg of elemental iron can be given in one dose (100ml
ns),over 30 mins,can be given 1-3 times /week or alternate days.

A total of 1.0gms can be given in 4-10 sittings (over 1 month )

F. Patient selection :

IV sucrose should be given only if hemoglobin levels are above 7gm%. In case of 7gm%
or below , transfusion should be considered

00 50
 G. Refractory cases: If hemoglobin levels do not improve > 3-4weeks, reevaluate cause.

Or consider blood transfusion .

H. Prerequistes-

Should be infused Under supervision

Keep emergency tray ready

I. Contraindications-

Iron overload,non iron deficiency anemia, known hypersensitivity

K. side effects -

Hypotension ,headache, vomiting ,nausea, dizziness ,joint

ache, parasthesia, abdominal and muscle pain, cardiovascular collapse(rare).

Ferrous Carboxy Maltose:

Ferric carboxymaltose , is a iron complex consisting of a ferric hydroxide core which is

stabilized by a carbohydrate shell, thus allowing for controlled delivery of iron to target
tissues.It is Administered intravenously, it is effective for iron-deficiency anaemia, treatment ,
delivers a replenishment dose of up to 1000 mg of iron during a minimum with in 15 minutes. It
is an effective option for iron-deficiency anaemia in those patients who are intolerant to oral
iron preparations.

Ferric carboxymaltose is a macromolecular ferric hydroxide carbohydrate complex, allowing

controlled delivery of iron in cells of the reticuloendothelial system and delivery to the iron-
binding proteins ferritin and transferrin.

00 51
 Intravenous administration of ferric carboxymaltose gives rise to transient elevations in serum
iron, serum ferritin and transferrin saturation, and in the corrects haemoglobin levels and also
replenishes depleted iron stores.

The total iron concentration in the serum increased rapidly in a dose-dependent manner after
intravenous administration of ferric carboxymaltose. Ferric carboxymaltose rapidly clears from
the circulation and is distributed to the bone marrow mainly 80% and to less extent spleen and
liver. Repeated weekly administration of ferric carboxymaltose are safe as it does not
accumulate transferrin iron in IDA patients.

“Ferric carboxy maltose was well tolerated in clinical trials in patients with iron-deficiency
anemia, with most drug-related adverse events considered to be mild to moderate in severity.
Commonly reported drug-related adverse events include headache, dizziness, nausea,
abdominal pain, constipation, diarrhea, rash and injection-site reactions. The incidence of drug-
related adverse events in patients receiving intravenous ferric carboxy maltose was generally
similar to that in patients receiving oral ferrous sulfate. In general, rash and local injection-site
reactions were more common with ferric carboxy maltose, whereas gastrointestinal adverse
events were more frequent with ferrous sulfate.” (103)

A retrospective case control study conducted in 2010-12 on 85 women, concluded that “ FCM
was effective in treating anemia in this population of pregnant women in the 3rd trimester and
appears to be safe for mother and child, although no definite conclusion about safety can be
drawn from the results of this small case group. A prospective randomized controlled trial is
warranted for a more detailed analysis on pregnancy outcomes.”(104).

Ferrous carboxy maltose has been included by ministry of health and family welfare ,
GOI , in a programme called intensified national iron plus initiative (I-NIPI) –operational
guidelines in a program called ‘anemia mukt bharat’ ,april 2018 .

 Blood transfusion: Severe anemia in last trimester needs blood transfusion,as iron
supplementation cannot replenish the iron stores.

00 52
 Royal college of obstetrician and gynaecologists (RCOG) blood transfusion guideline
,recommend immediate blood transfusion in labour or immediate postpartum period if
hb is < 7gm%.

Indications of blood transfusion recommended by FOGSI,2016 guidelines.

III. IMAGE
ANTEPARTUM PERIOD
1. Pregnancy <34 weeks
a. HB<5g/dL with or without signs of cardiac failure or hypoxia.
b. HB 5-7/dL in presence of impendind heart failure.

2. Pregnancy >34 weeks.

a. HB<7g/dL even with signs of cardiac failure or hypoxia.
b. Severe anemia with decompensation.

00 53
 MATERIALS AND METHODS

The study is titled prevalence of iron deficiency anemia in pregnancy and to study reponse
to the treatment with oral and parenteral iron.

Study design: Quasi Experimental study

Study setting: Tertiary care Hospital

Study period: 18 months from November 2017 to april 2019

Study population: Pregnant women with anemia

Inclusion criteria: Inclusion criteria

a) Pregnant woman with singleton pregnancy and with Hb less than 10.5 gm/dL
b) Age 18 to 45 years.
c) Gestational age between 24-34 weeks.
d) Booked cases.
e) Uncomplicated pregnancy by ruling out any medical/surgical illness and bleeding
disorder.

a) Exclusion Criteria: Chronic Medical diseases:- Congenital Heart Disease, Diabetes

Mellitus, chronic renal disorder.
b) Multiple pregnancies.
c) Patient with bleeding disorder.
d) Patient having history of Blood Tranfusion during present pregnancy,
hemoglobinopathies.
e) Infectious malaria, HIV, Kalaazar etc

Sample size: We conducted a pilot study to understand the prevalence of the iron deficiency
among pregnant women in 15 subjects. About 70% of the pregnant women were found to have

00 54
 iron deficiency; using this with 15% absolute error and 95% confidence interval, we found the
minimum sample size to be 36. For our convenience, we used 50 cases in the present study.

Sampling method: Simple random sampling in patient selection and further for division among
Group A and B it was done based on their willingness.

DATA COLLECTION : Patients are selected after explaining the detailed procedure. Written
informed valid consent was taken from pts recruited for studies . Patients were followed up
after 4 weeks of treatment with investigation report and then until delivery to check for
need of blood transfusion.
After confirming the diagnosis of iron deficiency anemia ,
Pt were divided into 2 groups :
A (n=A) - oral iron 60mg of elemental iron in BD doses ( few pts consumed ferrous
ascorbat3e and others ferrous sulphate )
B (n=B) - IV iron sucrose group

Visit 1 : Booked patients coming to OPD from 24-34weeks after thorough explaination and
consent were asked history regarding symptoms in detail. Patients fulfilling the inclusion
criteria were advised CBC with peripheral smear and hb electrophoresis .

Visit 2- pts with IDA identified on basis of investigations and symptoms and signs and all pts
diagnosed with IDA were given albendazole 400mg stat dose. (as per recommendations GOI
NIPI) for deworming.
And iron deficient pt were divided in group A and group B
group A received oral iron containg 60mg of elemental iron twice daily for 4 weeks .
and group B received iron sucrose IV after admission ,dose calculated from formula
mentioned above. Per day maximum 200mg infusion was given . No test dose given . Vial of
2.5/5 ml diluted in 0.9 % of 100ml normal saline and infused immediately after
preparation over not more than 30 mins .Emergency tray kept ready. Infusion was given
under supervision of a doctor . for any adverse reaction drip was immediately stopped and
treated .

00 55
 visit 3- pts with post treatment CBC were followed up in OPD after 4 weeks.
And asked questions about compliance , side effects .

Last follow up during/ immediately after delivery to check if blood transfusion was
required in either of the groups.

In our study , 7 patients, didn’t do advised investigations, hence were out from the study .
So study was conducted on 43 pts.
Statistical analysis:

The data was collected, compiled and analysed using EPI info (version 7.2). The qualitative
variables were expressed in terms of percentages. The quantative variables were both
categorised and expressed in terms of percentages or in terms of mean and standard
deviations. Difference between two proportions was analysed using chi square or fisher exact
test. All analysis was 2 tailed and the significance level was set at 0.05.

Ethical considerations:

Ethical committee clearance was taken before the start of the study. Written and informed
consent was taken from all the study subjects. The Study was further approved by the
university to be conducted in the hospital.

00 56
 Time frame of the study:

Literature search for research

topic June 2017

Topic selection – July 2017

Institutional Ethical Committee

clearance & Submission of
synopsis to university –
JANUARY 2017
Review of literature:
Data collection: June 2017 –
September 2019
After approval till
June 2019

Compilation and analysis of

data: till August 2019

Write up September 2019

Final Presentation October 2019

Submission- December 2019

00 57
 RESULTS AND ANALYSIS

• We included 50 cases in the present

1 study

• 7 cases were excluded in calculation of

prevalence
2 since all advised investigations were not done

• 32 cases had iron deficiency which were further

divided into two groups for the treatment
3 purpose

00 58
 TABLE 1. DISTRIBUTION OF CASES

IRON DEFICIENCY 32

NON IRON DEFICIENCY 11

EXCLUDED (N/A) - 07

TOTAL LEFT 43

CHART 1. DISTRIBUTION OF PATIENTS

7, 14%

IDA
11, 22% no IDA
N/A
32, 64%

00 59
 Table 2: Distribution of the study subjects based on the age group

Age group (years) Frequency Percentage

20 to 25 17 34.00

25 to 30 14 28.00

30 to 35 15 30.00

>35 4 8.00

Total 50 100.00

Mean 27.72

SD 5.30

Range 19 to 46

The mean age of the study subjects was 27.72 years with a range of 19 to 46 years in the
present study.

Chart 2: Distribution of the study subjects

based on the age group

34
20 to 25
30 25 to 30
30 to 35
>35

28

00 60
 Table 3: Distribution of the study subjects based on the gravida status

Gravida status Frequency Percentage

Multi 21 42.00

Primi 29 58.00

Total 100 100

About 42% were multi and 58% were primi in the present study.

Chart 3: Distribution of the study subjects

based on the gravida status

42

Multi
58
Primi

00 61
 Table 4: Distribution of the study subjects based on the Gestational age

Gestational age(weeks) Frequency Percentage

20 to 25 1 2.00

25 to 28 17 34.00

28 to 32 19 38.00

32 to 37 13 26.00

Total 50 100.00

Mean 28.57

SD 3.34

Range 21 to 34

The mean gestational age was 28.57 weeks with a range of 21 to 34 years in the present study.

Chart 4: Distribution of the study subjects

based on the Gestational age

26
34 20 to 25
25 to 28
28 to 32
32 to 37

38

00 62
 Table 5: Distribution of the study subjects based on the signs and symptoms (n=50)

Signs and symptoms Frequency Percentage

Generalised weakness 46 92.00

Loss of appetite 18 36.00

Pallor 43 86.00

Edema 12 24.00

Chart 5: Distribution of the study subjects based

on the signs and symptoms (n=50)
P 92
e 100 86
90
r
80
c
70
e 60
n 50 36
t 40 24
a 30
g 20
e 10
0
Generalised Loss of appetite Pallor Edema
weakness

00 63
 Table 6: Distribution of the study subjects based on the Hb Electro (n=43)

Hb Electrophoresis Frequency Percentage

Positive 3 6.98

Negative 40 93.02

Total 43 100.00

About 6.98% of the cases had positive for electrophoresis.

Chart 6: Distribution of the study subjects

based on the Hb Electro (n=43)

6.98

Positive
Negative

93.02

00 64
 Table 7: Distribution of the study subjects based on the iron deficiency (n=43)

Iron deficiency Frequency Percentage

Present 32 74.42

Absent 11 25.58

Total 43 100.00

Table 7: Distribution of the study subjects

based on the iron deficiency (n=43)

25.58

Present

74.42 Absent

00 65
 Table 8: Prevalence of iron deficiency among different parameters studied (n=43)

Parameters Iron deficiency P value

Present Absent

Nor % Nor %

Age group

20 to 25 11 34.38 4 36.36 0.9854

25 to 30 9 28.13 3 27.27

30 to 35 10 31.25 3 27.27

>35 2 6.25 1 9.09

Gravida status

Multi 14 93.33 1 6.67 0.0345

Primi 18 64.29 10 35.71

Gestational age

20 to 25 0 0 1 9.09 0.3235

25 to 28 12 37.50 4 36.36

28 to 32 10 31.25 4 36.36

32 to 37 10 31.25 2 18.18

There was no significant association between age group and gestational age with iron
deficiency in the present study. The prevalence of iron deficiency was significantly higher
among multigravida when compared to primigravida.

00 66
 Table 9: Various haematological parameter changes among both the groups (n=32)

Parameters Group

A P B P value
value
Pre Post Pre Post

Mean SD Mean SD Mean SD Mean SD

Haemoglobin 8.39 0.62 9.49 0.67 <0.001 8.28 0.59 10.41 0.67 <0.001

Hematocrit 25.83 2.31 27.69 2.55 <0.001 25.13 2.87 32.44 2.76 <0.001

MCV 69.63 4.86 73.19 4.00 <0.001 68.44 4.50 83.63 4.49 <0.001

% Change

Haemoglobin 13.11% 14.61%

Hematocrit 7.20% 29.08%

MCV 5.11% 22.19%

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 Chart 08: Various haematological parameter
changes among both the groups (n=32)
29.08%
30.00%

25.00% 22.19%

20.00%
14.61% Group A
15.00% 13.11%
Group B

10.00% 7.20%
5.11%
5.00%

0.00%
Haemoglobin Hematocrit MCV

00 68
 Table 10: Various complications among both the groups (n=32)

Complications Group P value

A B

Nor % Nor %

Nausea 6 37.50 2 12.50 0.1021

Vomiting 3 18.75 0 0 0.0688

Constipation 8 50.00 0 0 <0.001

Diarrhoea 3 18.75 0 0 0.0688

Gastritis 4 25.00 1 6.25 0.1441

Chart 09: Various complications among both the

groups (n=32)
50
50
P 45
e 37.5
40
r
35
c
30 25
e Group A
25 18.75 18.75
n Group B
20
t 12.5
15
a 6.25
10
g
5 0 0 0
e
0
Nausea Vomiting Constipation Diarrhoea Gastritis

00 69
 chart 10 . Complication Details

3
2.5
2
1.5
1
0.5
0
C C&G G&D G, C, N & N N,C N,V,C N,V,D T
V

Group A Group B

00 70
 TABLE 11. PATEINTS REQUIRING BLOOD TRANSFUSION IN GROUP A AND B

Blood transfusion Group P value

A oral iron B iron sucrose

Nor % Nor %
Yes 2 12.50 1 6.25 0.5441
No 14 88.50 15 93.75
Total 16 100.00 16 100.00

Chart 11: Requirement of blood transfusion among

the groups (n=32)
100%
90%
P
80%
e
r 70%
c 60%
e no
50%
n
40% yes
t
a 30%
g 20%
e
10%
0%
oral iron IV iron

00 71
 DISCUSSION

Anemia is a disease which is prevalent globally, And dominated by Iron deficiency anemia
especially more in developing countries like India. Iron deficiency during pregnancy is matter of
concern as it has deleterious effect not only on mother but also fetus. Iron deficiency in
pregnant woman is one of the common causes of maternal morbidity and mortality having its
adverse effect on perinatal outcome too. Many women attend antenatal opd in late pregnancy
or when anemia becomes symptomatic , by then it has become already severe. Pregnancy itself
causes dilutional anemia ,thereby decreasing the level of hemoglobin and iron stores in
maternal body and more during delivery landing up patient with iron deficiency anemia ,hence
pregnant woman require prophylactic oral iron supplementation to prevent effects of
dilutional anemia. However many patients are not compliant with oral iron supplementation
due to its gastrointestinal side effects and become defaulters ultimately establishing iron
deficiency in patients.

Various national programmes have also failed to reduce the prevalence of iron deficiency
anemia in pregnancy because of low efficacy of oral iron , more of side effects and difficulty to
achieve proper follow up and screening of all antenatal women time to time.

Hence in such a scenario , parenteral iron can bypass the side effects of oral iron , can
prevent IDA with lesser no. of visits, achieving satisfactory hemoglobin levels compared to oral
iron and reduce the no of blood transfusion .To implement proper management plan for iron
deficiency anemia and to check the effectivity of oral iron prophylaxis treatment, prevalence
should be known time to time in pregnant population. So that effective plan can be
implemented accordingly.

Therefore this study aims at studying the prevalence of iron deficiency anemia in
pregnancy and to compare the response of oral and parenteral iron .

In our study , amongst 50 patients , 7 patients were excluded as the advised investigation
were not done. ( table and chart 1 ). So the prevalence of iron deficiency anemia was
calculated from 43 patients , which is 74.41% (table and chart 8) . A similar study conducted in

00 72
 2006 , in 16 districts of India by G.S. Toteja et. all concluded prevalence of iron deficiency
anemia in pregnancy is 84.9% (n = 6,923) (105). A study conducted In 2010 in rural places of
India by Ahmad et all concluded prevalence of anemia in pregnancy as 74.8% which is alarming
(106) and a study conducted in northeast India in 2013 by R. Bora et all showed prevalence of
89.6% (107).

We included patients from 18 to 45 yrs. of age in our study from which , 17 pts are in age
group of 20-25 yrs. , 14 in 25-30yrs, 15 in 30-35yrs, 3in 35-40yrs age group , 1 in 40-45 yrs age
group. ( table 2 and chart 2 ). The mean age of patients in our study was 27.72 yrs. from which
in age group of 20-25 yrs. ,34.48%[ 11] are iron deficient , [28.13% [09] are iron deficient in age
group of 25-30 yrs. of age . In 30-35 yrs. age group 31.25% [10] are iron deficient , 6.25%[ 2 ] in
36-40 yrs. of age group, none in 40-45 yrs. of age group (table 8) .Although this carries no
significance statistically it is observed that maximum no of patients with IDA falls in category of
18-25yrs and 26-30yrs 40% and 30% respectively. It signifies that more of younger age group
population enter pregnancies with diminished iron stores , which is exacerbated by the time
2nd trimester of pregnancy. Study conducted in 2015 in Kolar taluka on 446 women by R
suryanarayana et all showed , prevalence of 66.1% in age group of 21-30 yrs (108)

Amongst 50 pts , 1 was in 20-25 weeks , 17 in 25-28 weeks,19 in 28-32 weeks and 13 in 32
to 37 weeks ( table 4 , chart 4 ) with mean gestational age of 28.5 weeks of which iron deficient
patients were classified again , in which no pt in 20-25 weeks , 37%[12] pts. in 25-28 weeks,
31.2% [10] in 28-32 weeks and 31.2 % [10] in 32-37weeks with P value of 0.32 which is
statistically not significant (table 8) but it was observed that rate of iron deficiency anemia
increased in 2nd trimester which marks the state of maximum hemodilution in pregnancy and
many women have first follow up in in late pregnancy after 28 weeks (table 4 , 8 and chart 4 )
Many studies, including that by Suryanarayana et al.(108) document an increase in anemia in
pregnant women with increasing gestational age. Where as in our study , on contrary , the
prevalence of anemia in the studied population decreased with an increase in the duration of
gestation after 30weeks although not statistically significant . A similar observation was also
made by Vemulapalli and Rao(109) in a study conducted in Andhra Pradesh where anemia was
documented least in the third trimester. The probable explanation is maximum patients seek

00 73
 antenatal care by 28weeks and receive oral iron prophylaxis and physiological anemia plateus
by 35weeks .

From 50 patients in study , 29 were primigravidas and 21 were multigravida .In our study
[29 ]58% were primigravidas and [21 ] 42% were multigravidas but it was also observed that
from 42% [ 21 ]multigravidas , almost all multigravida 93.33 % (14 from 15) (table 8) and
primigravidas were 64.29% (18 out of 28) were iron deficient , this analysis puts lights on two
facts, firstly more number of primigravidas are entering pregnancy with established anemia and
depleted iron stores and high prevalence of anemia in adult non pregnant women also ,which
strongly needs recognition of anemia pre pregnancy and prompt treatment for the same and
shorter interval between pregnancies predisposes women for iron deficiency anemia as body
cannot restore iron losses of previous pregnancy in short duration .Preconceptional CBC is
recommended by CDC (centre of disease control and prevention ) and WHO recommends
prompt management of anemia in adolescents only and government of India has launched a
programme for the same , NIPI (national iron plus initiative ) . Increasing gravidity and parity in
pregnant women was seen to be associated with an increase in the prevalence and severity of
anemia in the studied population . A similar observation was done by Hunshikatti and
Viveki(110)in a study where they concluded that the prevalence of anemia in pregnant women
increased with increasing parity.(table 3 , chart 3 , table 8)

In our study when patients were asked about symptoms 92 % [46]complained of generalised
weakness ; 36 % [18 ]complained loss of appetite and 4 patients had no complains out of
which 1 had iron deficiency anemia . Symptoms in iron deficiency are not reliable indicators to
know the onset of disease and is even more misleading if presents along with pregnancy as
pregnancy itself causes patients to experience weakness, fatigability and patients maximum
times do not have symptoms until the disease becomes severe . 86% [43] pt had palor and 24 %
[12] had odema . (table 5 and chart 5).

In our study mean gestational age at the time of inclusion in both groups is comparable (
in group A 29.12 and group B 28.31 ) in study conducted by shireen et all mean gestational age

00 74
 was 25.92 and 26.12 ingroup A and group B respectively ; in Aggarwal et all is 28 weeks and
28.2 weeks in both groups . (111)

In this study mean , mean pretreatment hemoglobin was 8.39+/- 0.62gm/dl in group A
and 8.275=/-0.59gm/dl in group B which is comparable and statistically insignificant between
the two groups , post treatment hemoglobin ,which was checked after 4 weeks showed a mean
value of 9.4+/-0.67 gm/dl in group A with a p value -<0.001 and 10.4 +/-0.67 gm/dl in group B
with p value of <0.001 which is statistically significant . The average rise of hemoglobin in group
A was 1.11 gm/dl and in group B it was 2.14gm/dl over a period of 4 weeks with p value of less
than <0.001 which is statistically insignificant but target value of 10.5 gm/dl is nearly achieved.
.The average rise of hemoglobin in randomized control trial conducted by Puneet Kaur
Kochhar et all published in 2013 ,3.1 g/dL in group A and 5.1 g/dL in group B; P = 0.002
(112) , study conducted by Shireen et all also shows the mean hemoglobin rise of 1.6gm/dl and
2.6gm/dl in each group respectively . Study conducted by Sunita VN et all concluded that
average rise of hemoglobin with parenteral iron sucrose was significantly high than oral iron at
end of 2nd week and 4th week.(113) Study by Mehta MN et al , showed in study that average
rise in hemoglobin with iron sucrose is better than that of oral iron ( average mean
pretreatment was 6.7gm/dl in iron sucrose and oral iron group and it rose to 10.64% and 10.1%
) (114) .In a study conducted by Meenal C et al average hemoglobin rise was 2- 2.9 g/dL in iron
sucrose group and whereas in oral iron group, average rise of 0.6-0.9g/ dL of Hemoglobin was
seen . Both group shows minor adverse drug reaction, IV iron sucrose can correct anemia in a
short period even in advanced pregnancy and prevent associated maternal and perinatal
complications. (115).(table 9 and chart 8 )

The mean baseline mean corpuscular volume (MCV) in group A and group B was 69.63 +/-
4.86 and group B 68.44 +/-4.5 and post treatment MCV was 73.19 +/-4 in group A with p value
of <0.001 and in group B 83.63+/-4.49, p value 0.001 with mean rise of 3.55 and 15.19 in both
groups A and B respectively and p value of < 0.001 which is statistically significant for both.
Study done by Neeru et all , showed increase in MCV by 5.47 in oral iron group and 10.21 in
iron sucrose group with p value of 0.008 which is again statistically significant .(116)(table 9 and
chart 8)

00 75
 The mean baseline hematocrit was 25.83+/-2.31 and 25.125 +/-2.87 in group A and group
B respectively with post treatment rise of 27.69+/-2.55 and 32.44+/-27 with a mean rise of 2.05
in group A and 7.32 in group B and p value < 0.001 which is statistically significant. ( table 09
and chart 8 ).

Though hemoglobin rose with with oral and parenteral iron both , but target value of
10.5gm/dl was achieved with parenteral iron in 4 weeks treatment and hematocrit and MCV
rise is significant in group B.

No serious side effects seen in both groups . Although Patients treated with oral iron
frequently complained of nausea, vomiting, diarrhea , constipation ,gastritis and few patients
who received parenteral iron sucrose complained of nausea . Of 32 patients , 11 pts in group A
complained of above sideeffects and 2 patients in group B complained of nausea following
administration of iron sucrose and 1 patient in group B had thrombophlebitis. 37.50% [6] pts
in group A and 12.5 % [ 2] in group B had complains of nausea , p value 0.1 not significant ,
18.7% [3 ] pts in group A complained of vomiting after consuming tablets ; 50% [8 ]patients
had constipation and 18.7% [ 3] complained of diarrhea and 25% [4] had gastritis leading them
to become defaulters of oral iron medicines ( table 11 and chart 10 ) . Similar observations
were seen in study conducted by al Momen et all(117), Al RA, Unlubilgin E et all(118). ( table
10,chart 9 and 10)

One of the objectives of our study was to check if parenteral iron treatment can reduce
number of emergency blood transfusion in pregnancy, delivery or postpartum but in our study
we couldn’t establish the relationship between parenteral iron sucrose and reduction in
number of blood transfusion , as 12.5% (2) pts in group A required blood transfusion and 6.25%
(1) patient in group B required blood transfusion with p value of 0.5 which is statistically
insignificant .However one study published by , Perewusnyk G, . British journal of nutrition.
2002 quotes “In cases of severe anaemia (haemoglobin <90 g/l) or non-response to parenteral
Fe after 2 weeks, recombinant erythropoietin is considered in combination. By using parenteral
Fe–sucrose in cases of severe Fe deficiency, anaemia during pregnancy is treated efficiently and

00 76
 safely according to our results and rate of blood transfusion could be reduced considerably to
below 1 % of patients per year.” . (table 11 and chart 11).

Bayoumeu F et all in a study conducted in 2005 , resulted in hemoglobin from 9.6 gm % to

11+/- 1.3 gm% iron sucrose group and and in oral group from 9.7 to 11+/-1.25 , statistically non
significant and ferritin values significantly high in iron sucrose group. ; and iron sucrose group
appears to be better for treatment without any serious sideeffects in correction of anemia in
pregnancy. (120)

Another study , by Gupta et all , concluded that hemoglobin rise in iron sucrose treatment is
significantly higher than oral iron group and can be beneficial in pregnant women with anemia
who present to OPD at later stages of pregnancy and tolerated iron sucrose well .(121)

Limitations in our study were , inadequate blood investigations specific to iron deficiency
anemia as the facility is not routinely available and are costly too.

00 77
 Conclusion

We come to following conclusion based on our study and after analyzing the data ,

1.) Prevalence of iron deficiency anemia in pregnancy in our study is 74.42 %.

2.) Prevalence of iron deficiency anemia is more in multigravidas (93.33%) compared to
primigravidas (64.29%)
3.) Prevalence of iron deficiency anemia in pregnancy is not age related.
4.) We couldn’t establish the relationship of prevalence of iron deficiency anemia and
gestational age as our study.
5.) Primigravidas comprised the maximum number of patients in both groups.
6.) Most of the pregnant women complained of generalised weakness .
7.) In both groups , all pts were pale on examination.
8.) The mean pretreatment hemoglobin in group A and B were 8.39g/dl and 8.28g/dl
respectively.
9.)The mean hemoglobin rise in group A and group B was 1.1gm/dl and 2.1 gm/dl
respectively . Significant MCV and hematocrit rise seen in both groups , but significant
in iron sucrose when compared to oral iron at the end of four weeks.
10.) None of the patients in IV iron sucrose group had a serious side effects, except one pt
who had thrombophlebitis.
11.) Significant number of patients in oral iron group had complains of constipation after
initiation of treatment.
12.) Three patients in study were hb electrophoresis positive .
13.) Two pts in oral iron group and 1 pt in IV iron sucrose group received blood transfusion ,
which was statistically insignificant and hence our study could not establish the
relationship of IV iron sucrose and blood transfusion.

00 78
 Summary

This study concluded , giving prevalence of iron deficiency anemia in pregnancy as 74.42%.
Intravenous iron sucrose and oral iron ; both treatments associated with rise in
hemoglobin,MCV and hematocrit but increment was more in intravenous group than oral iron
group. Patients with intravenous iron sucrose were benefited compared to oral iron in terms of
compliance and efficacy. Iv iron sucrose is better tolereated when compared to oral iron in
terms of sideeffects but Reduction in number of blood transfusion couldn’t be established with
IV iron sucrose .

Hence the hypothesis of , IV iron sucrose better than oral iron is proved.

00 79
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 ANNEXURE 1

DATA COLLECTION PROFORMA

Patient’s Name:

Age

Name of Head of the Family:

Address:

Contact No:

Patients Details:

Chief complains :

Menstrual History:

Last Menstrual Period: Expected Date of Delivery:

Obstetrics history :

Date of Marriage:

Gravida :

Present Pregnancy Complaints:

Oral folic acid supplementation : yes / no

Diet history : h/o pica / vegetarian/ non vegetarian food .

Personal history : bowel and bladder habbits

Medical history :

Surgical history :

h/o blood transfusion :

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 h/o of drug allergy :

Investigations advised :

Complete blood count

Platelet Count

Peripheral smear

Hb electrophoresis

And routine ANC profile

1. Fasting and post meal sugars

2. Urine routine and microscopy
3. Blood group and rh typing
4. VDRL
5. HIV / HBsAG / ANTI HCV

If clinically relevant ,
Stool routine and microscopy was advised
And additional iron studies were advised

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 ANNEXURE – 2
CONSENT (MARATHI)

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 CONSENT (HINDI)

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 INFORMED CONSENT

I Mrs. , give my consent to be included

in the academic study "Prevalence of anemia in
pregnancy and response to the treatment" to be
conducted during January 2018- December 2019. I have
been assured that no personal information will be
disclosed in the study, to anyone other than the experts
participating in the study. I have also been assured that,
without my permission, no medication or intervention
will be performed on me , which might cause any
physical/mental harm to me or my baby. I have been
explained the objectives and the need to perform this
study and I hereby give my consent voluntarily

Signature :
Name :
Date :
Place :

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KEY TO MASTER CHART

GA- gestational age

Primi- primigravida

Multi- multigravida

Symptoms –

GW-generalised weakness

LOA – loss of appetite

Signs-

P - palor

E- edema

HB-hemoglobin

MCV-mean corpuscular volume

Hct - hematocrit

Hb electro- hb electrophoresis

IDA-iron deficiency anemia

Group A-oral iron

Group b – iron sucrose

Complications /sideeffects -

N-Nausea

V-vomiting

G-gastritis

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 D-Diarrhea

C-constipation

T-Thrombophlebitis

BT – blood transfusions

Master chart used for study

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 MASTER CHART
Pre-Treatment Iron Grou Post-Treatment
OPD Symptom Complica
S No Age Gravida GA Signs Hb MCV HCt Hb Electro Deficie p Hb MCV HCt BT
No s ncy tion
A/B
10.
1 26 Primi 26 GW P 7.6 74 28 NEGATIVE YES A 9 80 30 NO NO
10.
2 22 Primi 28 GW P 9.1 67 26 NEGATIVE YES B 8 84 34 NO NO
3 24 Primi 28 GW NO 11 88 33 NEGATIVE NO - - - - - -
LOA
4 28 Multi 32 GW P+E 9.1 68 27 NEGATIVE YES A 9.8 72 29 N, C NO
5 30 Multi 30 GW P 8.1 65 26 NEGATIVE YES B 9.6 81 30 NO NO
LOA
6 22 Primi 28 GW P 7.9 66 25 NEGATIVE YES A 8.3 70 28 C NO
LOA
7 25 Multi 26 GW P+E 8 68 26 NEGATIVE YES B 9.5 80 30 NO NO
LOA
8 32 Multi 28 GW P+E 7.4 65 24 NEGATIVE YES A 8.9 70 27 NO NO
10.
9 46 Primi 29 GW P+E 5 86 32 NEGATIVE NO - - - - -
10.
10 28 Primi 25 GW P 8.4 66 25 NEGATIVE YES B 8 88 36 NO NO
11 30 Multi 28 GW P 9 70 24 NEGATIVE YES A 10 76 34 N,C NO
12 22 Primi 24 LOA P 9 71 25 NEGATIVE YES B 11 90 38 NO NO
GW
25. 12.
13 23 Primi 5 GW NO 3 88 34 NEGATIVE NO - - - - - -
LOA 10.
14 28 Primi 27 GW P+E 4 86 30 POSITIVE NO - - - - - -
15 24 Multi 33 NO P 8.4 76 28 NEGATIVE YES A 8.6 77 29 N,V,D YES
16 27 Primi 32 GW P 8.8 78 31 NEGATIVE YES B 9.8 86 30 NO NO
17 30 Primi 33 GW P+E 9.2 81 32 NEGATIVE YES A 10 80 31 N,C NO
10.
18 31 Multi 29 GW P 8.2 74 28 NEGATIVE YES B 2 84 34 T NO
11.
19 24 Primi 26 GW NO 5 88 33 NEGATIVE NO - - - - - -
20 22 Primi 32 GW NO 8 65 25 NEGATIVE YES A 10 71 28 NO NO
11.
21 21 Primi 24 GW P 8.4 66 25 NEGATIVE YES B 1 92 33 N NO
LOA
22 34 Multi 26 GW P+E 8 62 25 NEGATIVE YES A 9.1 73 25 N,V,C YES
23 30 Multi 25 LOA P 8 63 25 NEGATIVE YES B 9.8 78 29 NO NO

101
 GW
24 24 Multi 24 GW P 8.4 68 25 NEGATIVE YES A 9.6 68 26 C NO
LOA 11.
25 19 Primi 26 GW P 8.2 72 25 NEGATIVE YES B 2 85 35 NO NO
11.
26 25 Primi 25 NO NO 4 84 33 NEGATIVE NO - - - - - -
12.
27 28 Primi 28 NO NO 6 86 34 NEGATIVE NO - - - - - -
LOA
28 26 Multi 29 GW P+E 8.9 69 25 NOT DONE N/A - - - - - -
LOA
29 27 Primi 32 GW P+E 9.4 74 26 NEGATIVE YES A 10 76 28 G&D NO
30 34 Multi 31 GW P 9 72 26 NOT DONE N/A - - - - - -
31 38 Primi 28 GW P 9.2 74 28 NEGATIVE YES B 11 85 35 NO NO
32 22 Primi 26 GW P 8.8 70 25 NEGATIVE YES A 9 66 26 G&D NO
33 36 Multi 28 GW P 8.9 72 25 NOT DONE N/A - - - - - -
12.
34 32 Multi 33 NO NO 4 88 36 NEGATIVE NO - - - - - -
35 30 Primi 34 GW P 8 70 24 POSITIVE NO - - - - - -
LOA 10.
36 21 Primi 34 GW P 8.2 70 25 NEGATIVE YES B 5 80 30 NO NO

37 24 Multi 30 LOA P 8.2 70 24 NEGATIVE YES A 10 74 26 NO NO

GW
38 25 Multi 31 GW P 9 73 25 NOT DONE N/A - - - - - -
10.
39 28 Primi 34 GW P 7.8 66 20 NEGATIVE YES B 8 82 31 NO NO
40 34 Primi 28 GW P 8 67 24 NEGATIVE YES A 9.5 74 25 C&G NO
LOA
41 20 Primi 30 GW P 8.4 68 26 POSITIVE NO - - - - - -
42 24 Multi 32 GW P 9.8 78 28 NOT DONE N/A - - - - - -
10.
43 28 Multi 30 GW P 8.6 69 26 NEGATIVE YES B 6 84 30 NO NO
G, C,
44 30 Primi 34 GW P 9 72 26 NEGATIVE YES A 9.4 74 27 N&V NO
LOA
45 34 Primi 21 GW P 12 88 36 NEGATIVE NO - - - - - -
LOA 10.
46 36 Multi 34 GW P+E 7.4 65 20 NEGATIVE YES B 8 85 34 NO NO
LOA
47 32 Primi 26 GW P+E 7.8 66 22 NEGATIVE YES A 8.8 70 24 NO NO
LOA
48 26 Multi 24 GW P+E 7 61 21 NEGATIVE YES B 9 74 30 N YES
49 30 Multi 28 GW P 7.4 74 28 NOT DONE N/A - - - - - -
50 24 Primi 24 GW P 9.5 68 26 NOT DONE N/A - - - - - -

101