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DR ALKA MUKHERJEE
DR APURVA MUKHERJEE
NAGPUR M.S. INDIA
ADVANCES IN MANAGEMENT
OF ANAEMIA IN PREGNANCY
DR ALKA MUKHERJEE
MBBS DGO FICOG FICMCH PGDCR PGDMLS MA(PSY)
Director & Consultant At Mukherjee Multispecialty Hospital
MMC ACCREDITATED SPEAKER
MMC OBSERVER MMC MAO – 01017 / 2016
Present Position
 Director of Mukherjee Multispecialty Hospital
 Hon.Secretary INTERNATIONAL COUNCIL FOR HUMAN RIGHTS
 Hon.Secretary NARCHI NAGPUR CHAPTER (2018-2020)
 Hon.Secretary AMWN (2018-2021)
 Hon.Secretary ISOPARB (2019-2021)
 Life member, IMA, NOGS, NARCHI, AMWN & Menopause Society,
India, Indian medico-legal & ethics association(IMLEA), ISOPRB,
HUMAN RIGHTS
 Founder Member of South Rapid Action Group, Nagpur.
 On Board of Super Specialty, GMC, IGGMC, AIIMS Nagpur,
NKPSIMS, ESIS and Treasury, Nagpur for “ WOMEN SEXUAL
HARASSMENT COMMITTEE.”
mukherjeehospital@yahoo.com
www.mukherjeehospital.com
https://www.facebook.com/
Mukherjee Multispeciality
https://www.instagram.com/
Achievement
 Winner of NOGS GOLD MEDAL – 2017-18
 Winner of BEST COUPLE AWARD in Social
Work - 2014
 APPRECIATION Award IMA - MS
 Past Position
 Organizing joint secretary ENDO-GYN
2019
 Vice President IMA Nagpur (2017-2018)
Vice President of NOGS(2016-2017)
Organizing joint secretary ENDO-GYN
Organizing secretary AMWICON – 2019
INTRODUCTION
Globally, anaemia - most common complication in pregnancy – 51%
WHO - normal haemoglobin level in pregnancy – 11 gm%
8th leading cause of disease in girls and women,
> 40% non- pregnant women & > 50% pregnant women in the developing
world.
Obstetric practice in developing countries - high maternal morbidity
mortality and perinatal deaths.
Contributory factors - Poor Health Care Delivery System, Cultural Beliefs,
Poor Nutrition, Illiteracy, Gender Inequality, Teenage Pregnancies And High
Parity. Infections And Infestations
• Haemoglobin level below 11gm in pregnancy - anaemia.
• Developing countries the lower limit - 10 g/dl
(Large percentage of pregnant women in this setting with haemoglobin level of 10
g/dl tolerate pregnancy, labour and delivery very well and with good outcome)
HEMATOLOGICAL CHANGES IN PREGNANCY
• Pregnancy is associated with normal
physiological changes –
PREPARATION - 4 weeks of gestation
• Result of progesterone and
oestrogen.
• The total blood volume increases 35-
45 % above the non-pregnant level at
28 to 32 weeks.
• The plasma volume increases by 40-
45 % (1000mls).
• Red blood cell mass increases by 30-
33 % (approximately 300mg)
Gross iron demands
Obligatory Iron Loss (0.8mg × 290 days) 230 mg
Increase in red cell mass 450 mg
Newborn baby (birth weight 3.5 kg) 270 mg
Placenta and umbilical cord 90 mg
Blood loss at delivery 200 mg
Total gross 1240 mg
Net Iron demands
Absence of menstruation in pregnancy − 160 mg
Post partum decrease in red cell mass − 450 mg
Total net iron demands 630 mg
Approximate iron demands during a normal pregnancy and delivery
CLASSIFICATION OF ANAEMIA
• Etiology wise - Physiological (eg pregnancy) &
Pathological
• Based on red cell morphology - based on the size and shape of the
red blood cell,
1. Normocytic mcv80-90fl,
2. Macrocytic mcv>100fl,
3. Microcytic mcv<80fl)
• Based on pigmentation –
1. hyperchromic,
2. normochromic,
3. hypochromic)
• Anaemia be classified according to severity as mild,
moderate, severe and very severe
Degree of Severity Haemoglobin level (g/dl
Normal haemoglobin level >11g/dl
Mild Anaemia 9-11g/dl
Moderate 7-9g/dl
Severe 4-7g/dI
Very severe <4g/dl
AETIOLOGY
• The causes of anaemia in pregnancy - multifactorial.
• Major causes of anaemia in pregnancy
a. Nutritional deficiencies,
b. Infections and infestations,
c. Haemorrhage and
d. Haemoglobinathies.
e. Chronic medical disorders like renal and hepatic
diseases.
• A. Haemorrhagic:
• i. Antepartum
haemorrhage
• (eg placenta praevia ,
abruptio
• placenta)
• ii. Intrapartum
haemorrhage
• b. Chronic
• i. Hookworm infestation
• ii. Bleeding hemorrhoids
• iii. Peptic Ulcer Disease
• B. Nutritional Anaemia
• i. Iron deficiency
• ii. Folate deficiency
• iii. B12 deficiency
• C. Bone marrow failure
• a. Aplastic anaemia
• b. Isolated secondary
failure of
erythropoiesis
• c. Drugs (eg
Chloramphenicol,
Zidovudine
• C. Haemolytic
• a. Inherited
• i.Haemoglobinopathies
( eg Sickle cell
disorders,
• Thalassemia)
• ii. Red cell Membrane
defects ( eg Hereditary
spherocytosis,
• elliptocytosis)
• iii. Enzyme deficiencies
(eg G6PD deficiency,
Pyruvate kinase
• defeciency)
Acquired
i. Immune Haemolytic
anaemias ( eg autoimmune,
alloimmune, drug induced)
ii. Non- Immune Haemolytic
anaemias
a. Acquired membrane defects
(eg
Paroxysmal nocturnal
Haemoglobinuria)
b.Mechanical damage ( eg
Microangiopathic haemolytic
anaemia)
• iii Secondary to
systemic disease
• (eg renal diseases,
liver disease)
• iv.Infections
(Malaria, Sepsis,
HIV)
• Blood loss anemia
• Anemia of chronic
disease
• myelodysplasia
• Hereditary
spherocytosis
• Haemoglobinopathies
• Normocytic
Normochromic
• Autoimmune
haemolytic anaemia
• Systemic Lupus
Erythomatosis
• Collagen vascular
disorders
• Bone marrow failure
• Malignancies
A. Hypochromic
Microcytic
o Iron deficiency
o Thalassemia
o Sideroblastic
anemia
o Anaemia of
chronic disorders
o Lead poisoning
B. Macrocytic
Folic acid deficiency
Vitamin B12 deficiency
Liver disease
Myxoedema
Chronic Obstructive
Pulmonary Disease
Myelodysplastic
syndromes
Blood loss anemia
NUTRITION
Nutritional
deficiency major
cause of anaemia
in pregnancy.
Who - half of all
pregnant women
suffer
Mainly due iron
and folate
deficiency in diet.
Diseases that
cause poor
dietary intake or
malabsorption of
these nutrients
will also result in
nutritional
anaemia.
NUTRITION
• The demand for iron increases in pregnancy as it is required by both
mother and fetus for growth and development.
• In developing countries the already depleted iron stores as a result of
poor diet, too early, too many and too frequent, Hook worm
infestation
• The folic acid requirement is also increased two fold in pregnancy.
Normal body stores can only last for 3- 4 months
• Folate deficiency - Ineffective erythropoiesis, increased haemolysis
- Poor dietary intake, excess utilization
- Exacerbated in hemoglobinopathies & malaria
• Vitamin B12 is rare during pregnancy as the daily requirement is as low as 3-
5µg and liver stores last for as long as 2 years
INFECTIONS
Pregnant women are
more prone - depressed
immunity.
Anaemia due to
infections is usually
as a result of
products from the
infecting organisms
causing ill health,
fever, red cell
destruction and/ or
reduced red cell
production.
Bacterial infections
used to be a leading
cause of anaemia,
Tropics and
developing countries
– Malaria
&
HIV - AIDs
HAEMOGLOBINOPATHIES - chronic haemolytic anaemia
• The haemoglobinopathies that cause anaemia in pregnancy
• sickle cell disorders- HbSS, HbSC and
• HBS-β thalassemia.
• In sickle cell disorders, the abnormal haemoglobin S sickles
in hypoxic states, predisposing the structurally damaged
cells to early destruction hence affected persons are
chronically anaemic.
• Folate demands are increased and concurrent infections will
worsen anaemia
Risk factors for anaemia in pregnancy
Fetal Maternal
CONSEQUENCES OF ANEMIA IN PREGNANCY
HISTORY
• A detailed history including
i. Diet & feeding habits
ii. Gynaecological,
iii. Obstetric,
iv. Drug and social history should be taken.
v. It is also important to enquire in detail about duration
and symptoms of anaemia (if any), symptoms of
decompensation and possible predisposing factors.
CLINICAL FEATURES
INVESTIGATIONS
• CBC Hb PCV TLC DLC PS – type of anemia, parasite
• Red cell indices include mean corpuscular volume (MCV), mean
corpuscular haemoglobin (MCH) and mean corpuscular
haemoglobin concentration (MCHC).
• These indices will classify anaemia into either microcytic (MCV
<80 fL),
• macrocytic (MCV >100fL) and
• normocytic (MCV80-100fL) or
• hypochromic or normochromic (MCH and MCHC).,
• A peripheral blood smear and reticulocyte count are also
mandatory.
• Stool
Normal range Clinical utility
%HypoM < 3.4% Indicator of IDA
%HypoR < 3.7% Indicator of IDA
CHr < 25 pg Measures functional
iron available over 3–
4 days, early indicator
of IDA and response to
iron therapy
MH < 3.7 Differentiating IDA from
Beta Thalassemia trait
Newer RBC parameters for IDA
%HypoM %Hypochromic microcytes; %HypoR %Hypochromic reticulocytes;
CHr reticulocyte hemoglobin content;
M/H Microcytic RBC%/Hypochromic RBC%
LAB.DIAGNOSIS OF CAUSE(S) OF ANAEMIA
10–30 μM/L
20–200
> 16 to < 45
Serum Ferritin
• Serum ferritin is a more sensitive and specific
marker for ID - Low Serum Ferritin Values - the
best test for confirmation of IDA in pregnancy.
• During pregnancy, in women with adequate
iron stores, serum ferritin initially rises and
later gradually falls to about 50% of pre
pregnancy levels by 32 weeks (due to
hemodilution), followed by a slight rise in the
third trimester
• A pre pregnancy cut off < 70μg/dl to be
predicative of development of IDA in
pregnancy
Bone marrow
stainable iron
stores - the
gold standard
but
INVASIVE
AND
IMPRACTICAL
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
Indications of testing serum ferritin in pregnancy
Diagnosing ID in the Setting of Inflammation
In the setting of inflammation (e.g. post-operative state) or infection during pregnancy, serum
ferritin may be falsely elevated concomitant with CRP levels . Serum ferritin levels also exhibit a
post-partum rise consequent to inflammation and are no longer representative of iron status
• 2. Haemoglobinopathies
• a. Hb electrophoresis
• 3. HIV infection
• a. Detection of antibody to
• HIV using ELISA or
• Western blot assays.
• 4. Chronic medical
disorders
• a. Liver function tests
• b. Serum electrolyte,
• urea and creatinine
• c. Screening for
• autoimmune diseases
• 5. Antepartum
haemorrhage
• a. Ultrasonography
Management of anemia in pregnancy
Dietary Recommendations
• RDA of iron in third trimester - 30 mg/day.
• The average iron density in an average Indian diet is
8.5 mg/1000 KCal and the average iron absorption
from a rice based and wheat based Indian diet in
pregnancy is 13.3 and 5.3% respectively
• Dietary modifications are cheap and culturally
acceptable.
• Dietary modifications - inadequate and most
pregnant women require supplementary iron.
PREVENTION OF ANAEMIA IN PREGNANCY
• Pre-pregnancy counselling and dietary advice
• Rich sources of iron include haeme iron (in meat, poultry, fish and
egg yolk), dry fruits, dark green leafy vegetables (spinach, beans,
legumes, lentils) and iron fortified cereals.
• Using cast iron utensils for cooking and taking iron with vitamin C
(orange juice) can improve its intake and absorption.
• Avoid foods which may inhibit iron absorption - polyphenols (in
certain vegetables, coffee), tannins (in tea), phytates (in bran) and
calcium (in dairy products)
• CBC at the booking and at 28 weeks in pregnancy to screen for
anaemia.
• Repeat Hb near term in high risk mothers and multiple
pregnancies
Preventing IDA in Pregnancy
• The CDC recommends - 30 mg per day iron supplement at the
first prenatal visit
• WHO recommends - 30–60 mg per day of elemental iron for all
pregnant women
• National iron plus initiative recommends iron folic acid [IFA]
supplementation of 100 mg elemental iron and 500 μg of folic
acid every day for at least 100 days starting after the first
trimester at 14–16 weeks of gestation for all non-anemic
pregnant women followed by the same dose for 100 days
postpartum
Medication/food that inhibits iron absorption
Full stomach
Milk, calcium rich foods, antacids containing calcium, soy products, calcium
supplements
Foods high in fibre including bread, grains, cereals
Caffeine containing substances including chocolate, coffee, tea
Multivitamins, zinc and magnesium
Proton pump inhibitors, H2 receptor antagonists
Tetracycline
Thyroxine
Iron inhibits medication absorption
Antibiotics (tetracycline)
Methyldopa
Dolutegravir
Quinolones
Food or medications that may be used in pregnancy that
inhibit iron absorption, or whose action may be inhibited by iron
Parenteral Iron Therapy
• Intramuscular (IM) Iron
• The Ministry of Health and Family Welfare guidelines :
• Recommend IM iron following a test dose as a cost-effective treatment
for moderate anemia in pregnancy
Risks - Inconvenience of painful injection,
Dark discoloration of the skin, and
The risk of myalgias, arthritis, hypersensitivity, lymphadenopathy
Increased risk of development of sarcoma at the site of injection in treated animals
Low molecular weight iron dextran is the only preparation which can be recommended for
intra muscular use in primary care settings with a Z technique if resuscitation facilities are
available
Intravenous iron
One of the previous disadvantage of IV iron was the requirement of multiple
infusions.
But now iron-isomaltoside and iron carboxymaltose which allow larger
infusion doses of elemental iron to be administered over a short period of
time
Advantages:
• Complete bioavailability
with
• Fewer GI side effects and
• Faster recovery of hb than
oral iron.
Disadvantages:
• The increased risk of oxidant
damage,
• Increased cost and
• Small but finite risk of
hypersensitivity reaction limit
the widespread use of IV iron
Precautions for IV Iron
• Parenteral iron should always be administered once ID is confirmed using
serum ferritin or other specific investigations,
• An informed consent at a center where resuscitation facilities are available.
• Vitals should be checked periodically during and at the end of infusion by a
physician, nurse or trained mid wife.
• A test dose is required only for LMW iron Dextran while other parenteral
iron preparations do not require test dosing.
• Patient should be explained about the transient side effects of IV iron
supplementation include nausea, vomiting, pruritus, headache, and
flushing;
• Myalgia, arthralgia, and back and chest pain that usually resolve within
48 h of infusion
• Ganzoni's equation calculating the dose of par enteral iron in pregnancy is :
• Required iron dose[mg] = [2.4×[target hb−actual hb] ×pre –
pregnancy weight [kg]] +1000mg for replenishment of stores
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
Indications and contraindications of using IV iron in pregnancy
Assessing Response to iron
Increase in reticulocyte Hb
content (CHr) is the earliest
marker of response as early
as 3 days.
It requires validation in
pregnancy and is not widely
available currently
A rise in hemoglobin by 1 g/dl is
expected at the end of 2 weeks
and by 2 g/dl by the end of
4 weeks in the absence of other
micronutrient deficiencies and
ongoing blood loss for patients
on oral iron
A suboptimal rise is an
indication for checking
compliance, reconfirmation
of diagnosis and
consideration for parenteral
iron therapy.
Once the Hb is in normal range,
100–200 mg/day of iron should
continue for at least 3 months and
at least 6 weeks postpartum to
replenish the stores and 60–
100 mg/d oral iron should
continue for at least 3–6 months
postpartum
Postpartum Anemia
Associated with poor quality of life (QOL) and increased rates of depression in women
Routine postpartum prophylaxis by WHO recommended doses of 60 mg/d for three months or
mohfw doses of 100 mg/d to non-anemic women for 6 months has been shown to be cost
effective in decreasing the rates of anemia in our country.
It should be reinforced at the time of discharge from health care facility to the lactating mother
Hemoglobin should be checked in all women where estimated blood loss is > 500 ml within
48 h of delivery or in women known to have antepartum anemia or having symptoms of
anemia .
While mildly symptomatic women can be treated with therapeutic oral iron at the dose of 100–
200 mg/d for next 3 months, iv iron can be considered in moderate anemia
In case of severe anemia or evidence of hemodynamic comprise patients should receive
transfusion prior to discharge from health facility. Wherever feasible, a follow up CBC with
serum ferritin should be considered before discontinuation of iron therapy at 3 to 6 months.
Role of Erythropoietin
• Recombinant human erythropoietin (RhuEPO) has
been shown to be safe and effective for the rapid
correction of severe peripartum anemia in
conjunction with IV iron, particularly in cases with
antepartum and postpartum hemorrhage and
patients with rare blood groups.
• Insufficient evidence for routine use of EPO in
pregnancy except in cases with renal disease
• Erythropoietin 100-200U/Kg 3times a week until normalization of the
red cell and then once a weekly to maintain haemoglobin of
approximately 12g/dl.
Role of Transfusion
• Transfusion in pregnancy carries additional risks :
 RBC allo-immunization,
 volume overload and
 fetal hemolytic disease.
 The current AABB and the RCOG guidelines suggest a threshold of
Hb < 7 g/dl for transfusion and a threshold of < 8 g/dl in patients
with pre-existing cardiovascular disease
• The decision of transfusion should be individualized depending on
available alternatives of oral and parenteral iron, present and
future risk of hemorrhage, comorbidities like DIC,
thrombocytopenia, acuteness of fall in Hb and cardiovascular
status.
• Partial exchange transfusion has not been shown to be superior to
transfusion under diuretic cover for patients who present with
severe anemia and congestive cardiac failure at term
Indications of blood transfusion in pregnancy with IDA
Antepartum period Intrapartum period Post partum period
1. Pregnancy < 36 weeks
a. Hb < 4 g/dL with or without
signs of cardiac failure or hypoxia
b. 5–7 g/dL with presence of
impending heart
failure,hemodynamic instability or
acute 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
a. Hb < 7 g/dL[in labor]
[Decision of blood
transfusion depends on
medical history or
symptoms]
b. Severe anemia with
decompensation or
acute hemorrhage with
decompensation
a. Anemia with signs of
shock/acute hemorrhage
with signs of
hemodynamic instability
b. Hb < 7gm %:Decision
of transfusion depends
on medical history or
symptoms
Management of Labor in Patients with Anemia
Heavier blood loss –
 Increasing use of regional anaesthesia,
 Use of upright position during delivery,
 Manual removal of placenta and episiotomy
• All patients with anemia should preferably undergo delivery
where facility of blood transfusion and intra venous access are
available.
• Cross matched blood units should be kept reserved in patients
with moderate to severe anemia undergoing delivery.
• In all anemic patients with pregnancy active management of
third stage of labor with the use of syntocin or misoprostol is
effective in reducing the blood loss and should be practiced
Role of Deworming
• WHO recommends routine deworming using single dose
Albendazole (400 mg) or mebendazole (500 mg) in all
pregnant patients after first trimester in areas where both
baseline prevalence of hookworm/Trichuris Trichura
infection is > 20% and prevalence of anemia in pregnant
women is > 40% and is therefore applicable to India.
• Infected women in non endemic areas should receive anti-
helmenthic treatment on a case to case basis. The safety of
anti-helmenthic agents in pregnancy have not been
unequivocally established however deworming is advocated
in regions where benefits outweigh the risks
Treatment of anaemia from folate
deficiency
Folic acid 5mg daily for 4 months and is
usually given throughout pregnancy.
Vitamin B12 deficiency is rare in pregnancy
and is treated with intramuscular injections
of hydroxocobalamin 1000ug .
Initial doses are 6 injections over 2-3 weeks
then 100ug every 3 months
Other Treatment
• Treatment of malaria with artemisin combination
therapy,
• Bacterial infections with appropriate antibiotics,
• Hookworm infestation with mebendazole or
albendazole and
• Use of highly active antiretroviral therapy according
to treatment guidelines in HIV infection.
• Other co-morbidities e.G. Diabetes, hypertension
should also be managed.
Conclusions and Future Vision
• IDA in pregnancy is readily manageable yet an unmet health demand.
• The management strategy is dependent upon the period of gestation
and severity of anemia.
• Widespread implementation of preventive and therapeutic strategies is
still lacking in our country.
• Organization of awareness camps, patient group meetings and the use of
social media can spread awareness of this public health issue.
• “National Anemia Awareness and Treatment Day” with countrywide
participation of health care personnel to target the vulnerable groups
specially the pregnant women and teenagers of the country. The day can
be used as a platform not only to disseminate knowledge regarding the
consequences of anemia on feto-maternal and adolescent health but
also to deliver cheap and easy treatment options available for the same.
Management of anaemia in pregnancy BY DR ALKA MUKHERJEE DR APURVA MUKHERJEE NAGPUR M S INDIA

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Management of anaemia in pregnancy BY DR ALKA MUKHERJEE DR APURVA MUKHERJEE NAGPUR M S INDIA

  • 1. DR ALKA MUKHERJEE DR APURVA MUKHERJEE NAGPUR M.S. INDIA ADVANCES IN MANAGEMENT OF ANAEMIA IN PREGNANCY
  • 2. DR ALKA MUKHERJEE MBBS DGO FICOG FICMCH PGDCR PGDMLS MA(PSY) Director & Consultant At Mukherjee Multispecialty Hospital MMC ACCREDITATED SPEAKER MMC OBSERVER MMC MAO – 01017 / 2016 Present Position  Director of Mukherjee Multispecialty Hospital  Hon.Secretary INTERNATIONAL COUNCIL FOR HUMAN RIGHTS  Hon.Secretary NARCHI NAGPUR CHAPTER (2018-2020)  Hon.Secretary AMWN (2018-2021)  Hon.Secretary ISOPARB (2019-2021)  Life member, IMA, NOGS, NARCHI, AMWN & Menopause Society, India, Indian medico-legal & ethics association(IMLEA), ISOPRB, HUMAN RIGHTS  Founder Member of South Rapid Action Group, Nagpur.  On Board of Super Specialty, GMC, IGGMC, AIIMS Nagpur, NKPSIMS, ESIS and Treasury, Nagpur for “ WOMEN SEXUAL HARASSMENT COMMITTEE.” mukherjeehospital@yahoo.com www.mukherjeehospital.com https://www.facebook.com/ Mukherjee Multispeciality https://www.instagram.com/ Achievement  Winner of NOGS GOLD MEDAL – 2017-18  Winner of BEST COUPLE AWARD in Social Work - 2014  APPRECIATION Award IMA - MS  Past Position  Organizing joint secretary ENDO-GYN 2019  Vice President IMA Nagpur (2017-2018) Vice President of NOGS(2016-2017) Organizing joint secretary ENDO-GYN Organizing secretary AMWICON – 2019
  • 3. INTRODUCTION Globally, anaemia - most common complication in pregnancy – 51% WHO - normal haemoglobin level in pregnancy – 11 gm% 8th leading cause of disease in girls and women, > 40% non- pregnant women & > 50% pregnant women in the developing world. Obstetric practice in developing countries - high maternal morbidity mortality and perinatal deaths. Contributory factors - Poor Health Care Delivery System, Cultural Beliefs, Poor Nutrition, Illiteracy, Gender Inequality, Teenage Pregnancies And High Parity. Infections And Infestations • Haemoglobin level below 11gm in pregnancy - anaemia. • Developing countries the lower limit - 10 g/dl (Large percentage of pregnant women in this setting with haemoglobin level of 10 g/dl tolerate pregnancy, labour and delivery very well and with good outcome)
  • 4. HEMATOLOGICAL CHANGES IN PREGNANCY • Pregnancy is associated with normal physiological changes – PREPARATION - 4 weeks of gestation • Result of progesterone and oestrogen. • The total blood volume increases 35- 45 % above the non-pregnant level at 28 to 32 weeks. • The plasma volume increases by 40- 45 % (1000mls). • Red blood cell mass increases by 30- 33 % (approximately 300mg)
  • 5. Gross iron demands Obligatory Iron Loss (0.8mg × 290 days) 230 mg Increase in red cell mass 450 mg Newborn baby (birth weight 3.5 kg) 270 mg Placenta and umbilical cord 90 mg Blood loss at delivery 200 mg Total gross 1240 mg Net Iron demands Absence of menstruation in pregnancy − 160 mg Post partum decrease in red cell mass − 450 mg Total net iron demands 630 mg Approximate iron demands during a normal pregnancy and delivery
  • 6. CLASSIFICATION OF ANAEMIA • Etiology wise - Physiological (eg pregnancy) & Pathological • Based on red cell morphology - based on the size and shape of the red blood cell, 1. Normocytic mcv80-90fl, 2. Macrocytic mcv>100fl, 3. Microcytic mcv<80fl) • Based on pigmentation – 1. hyperchromic, 2. normochromic, 3. hypochromic)
  • 7. • Anaemia be classified according to severity as mild, moderate, severe and very severe Degree of Severity Haemoglobin level (g/dl Normal haemoglobin level >11g/dl Mild Anaemia 9-11g/dl Moderate 7-9g/dl Severe 4-7g/dI Very severe <4g/dl
  • 8. AETIOLOGY • The causes of anaemia in pregnancy - multifactorial. • Major causes of anaemia in pregnancy a. Nutritional deficiencies, b. Infections and infestations, c. Haemorrhage and d. Haemoglobinathies. e. Chronic medical disorders like renal and hepatic diseases.
  • 9. • A. Haemorrhagic: • i. Antepartum haemorrhage • (eg placenta praevia , abruptio • placenta) • ii. Intrapartum haemorrhage • b. Chronic • i. Hookworm infestation • ii. Bleeding hemorrhoids • iii. Peptic Ulcer Disease • B. Nutritional Anaemia • i. Iron deficiency • ii. Folate deficiency • iii. B12 deficiency • C. Bone marrow failure • a. Aplastic anaemia • b. Isolated secondary failure of erythropoiesis • c. Drugs (eg Chloramphenicol, Zidovudine • C. Haemolytic • a. Inherited • i.Haemoglobinopathies ( eg Sickle cell disorders, • Thalassemia) • ii. Red cell Membrane defects ( eg Hereditary spherocytosis, • elliptocytosis) • iii. Enzyme deficiencies (eg G6PD deficiency, Pyruvate kinase • defeciency)
  • 10. Acquired i. Immune Haemolytic anaemias ( eg autoimmune, alloimmune, drug induced) ii. Non- Immune Haemolytic anaemias a. Acquired membrane defects (eg Paroxysmal nocturnal Haemoglobinuria) b.Mechanical damage ( eg Microangiopathic haemolytic anaemia) • iii Secondary to systemic disease • (eg renal diseases, liver disease) • iv.Infections (Malaria, Sepsis, HIV) • Blood loss anemia • Anemia of chronic disease • myelodysplasia • Hereditary spherocytosis • Haemoglobinopathies
  • 11. • Normocytic Normochromic • Autoimmune haemolytic anaemia • Systemic Lupus Erythomatosis • Collagen vascular disorders • Bone marrow failure • Malignancies A. Hypochromic Microcytic o Iron deficiency o Thalassemia o Sideroblastic anemia o Anaemia of chronic disorders o Lead poisoning B. Macrocytic Folic acid deficiency Vitamin B12 deficiency Liver disease Myxoedema Chronic Obstructive Pulmonary Disease Myelodysplastic syndromes Blood loss anemia
  • 12. NUTRITION Nutritional deficiency major cause of anaemia in pregnancy. Who - half of all pregnant women suffer Mainly due iron and folate deficiency in diet. Diseases that cause poor dietary intake or malabsorption of these nutrients will also result in nutritional anaemia.
  • 13. NUTRITION • The demand for iron increases in pregnancy as it is required by both mother and fetus for growth and development. • In developing countries the already depleted iron stores as a result of poor diet, too early, too many and too frequent, Hook worm infestation • The folic acid requirement is also increased two fold in pregnancy. Normal body stores can only last for 3- 4 months • Folate deficiency - Ineffective erythropoiesis, increased haemolysis - Poor dietary intake, excess utilization - Exacerbated in hemoglobinopathies & malaria • Vitamin B12 is rare during pregnancy as the daily requirement is as low as 3- 5µg and liver stores last for as long as 2 years
  • 14. INFECTIONS Pregnant women are more prone - depressed immunity. Anaemia due to infections is usually as a result of products from the infecting organisms causing ill health, fever, red cell destruction and/ or reduced red cell production. Bacterial infections used to be a leading cause of anaemia, Tropics and developing countries – Malaria & HIV - AIDs
  • 15. HAEMOGLOBINOPATHIES - chronic haemolytic anaemia • The haemoglobinopathies that cause anaemia in pregnancy • sickle cell disorders- HbSS, HbSC and • HBS-β thalassemia. • In sickle cell disorders, the abnormal haemoglobin S sickles in hypoxic states, predisposing the structurally damaged cells to early destruction hence affected persons are chronically anaemic. • Folate demands are increased and concurrent infections will worsen anaemia
  • 16. Risk factors for anaemia in pregnancy
  • 17. Fetal Maternal CONSEQUENCES OF ANEMIA IN PREGNANCY
  • 18. HISTORY • A detailed history including i. Diet & feeding habits ii. Gynaecological, iii. Obstetric, iv. Drug and social history should be taken. v. It is also important to enquire in detail about duration and symptoms of anaemia (if any), symptoms of decompensation and possible predisposing factors.
  • 20. INVESTIGATIONS • CBC Hb PCV TLC DLC PS – type of anemia, parasite • Red cell indices include mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC). • These indices will classify anaemia into either microcytic (MCV <80 fL), • macrocytic (MCV >100fL) and • normocytic (MCV80-100fL) or • hypochromic or normochromic (MCH and MCHC)., • A peripheral blood smear and reticulocyte count are also mandatory. • Stool
  • 21. Normal range Clinical utility %HypoM < 3.4% Indicator of IDA %HypoR < 3.7% Indicator of IDA CHr < 25 pg Measures functional iron available over 3– 4 days, early indicator of IDA and response to iron therapy MH < 3.7 Differentiating IDA from Beta Thalassemia trait Newer RBC parameters for IDA %HypoM %Hypochromic microcytes; %HypoR %Hypochromic reticulocytes; CHr reticulocyte hemoglobin content; M/H Microcytic RBC%/Hypochromic RBC%
  • 22. LAB.DIAGNOSIS OF CAUSE(S) OF ANAEMIA 10–30 μM/L 20–200 > 16 to < 45
  • 23. Serum Ferritin • Serum ferritin is a more sensitive and specific marker for ID - Low Serum Ferritin Values - the best test for confirmation of IDA in pregnancy. • During pregnancy, in women with adequate iron stores, serum ferritin initially rises and later gradually falls to about 50% of pre pregnancy levels by 32 weeks (due to hemodilution), followed by a slight rise in the third trimester • A pre pregnancy cut off < 70μg/dl to be predicative of development of IDA in pregnancy Bone marrow stainable iron stores - the gold standard but INVASIVE AND IMPRACTICAL
  • 24. 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 Indications of testing serum ferritin in pregnancy Diagnosing ID in the Setting of Inflammation In the setting of inflammation (e.g. post-operative state) or infection during pregnancy, serum ferritin may be falsely elevated concomitant with CRP levels . Serum ferritin levels also exhibit a post-partum rise consequent to inflammation and are no longer representative of iron status
  • 25. • 2. Haemoglobinopathies • a. Hb electrophoresis • 3. HIV infection • a. Detection of antibody to • HIV using ELISA or • Western blot assays. • 4. Chronic medical disorders • a. Liver function tests • b. Serum electrolyte, • urea and creatinine • c. Screening for • autoimmune diseases • 5. Antepartum haemorrhage • a. Ultrasonography
  • 26. Management of anemia in pregnancy
  • 27. Dietary Recommendations • RDA of iron in third trimester - 30 mg/day. • The average iron density in an average Indian diet is 8.5 mg/1000 KCal and the average iron absorption from a rice based and wheat based Indian diet in pregnancy is 13.3 and 5.3% respectively • Dietary modifications are cheap and culturally acceptable. • Dietary modifications - inadequate and most pregnant women require supplementary iron.
  • 28. PREVENTION OF ANAEMIA IN PREGNANCY • Pre-pregnancy counselling and dietary advice • Rich sources of iron include haeme iron (in meat, poultry, fish and egg yolk), dry fruits, dark green leafy vegetables (spinach, beans, legumes, lentils) and iron fortified cereals. • Using cast iron utensils for cooking and taking iron with vitamin C (orange juice) can improve its intake and absorption. • Avoid foods which may inhibit iron absorption - polyphenols (in certain vegetables, coffee), tannins (in tea), phytates (in bran) and calcium (in dairy products) • CBC at the booking and at 28 weeks in pregnancy to screen for anaemia. • Repeat Hb near term in high risk mothers and multiple pregnancies
  • 29. Preventing IDA in Pregnancy • The CDC recommends - 30 mg per day iron supplement at the first prenatal visit • WHO recommends - 30–60 mg per day of elemental iron for all pregnant women • National iron plus initiative recommends iron folic acid [IFA] supplementation of 100 mg elemental iron and 500 μg of folic acid every day for at least 100 days starting after the first trimester at 14–16 weeks of gestation for all non-anemic pregnant women followed by the same dose for 100 days postpartum
  • 30. Medication/food that inhibits iron absorption Full stomach Milk, calcium rich foods, antacids containing calcium, soy products, calcium supplements Foods high in fibre including bread, grains, cereals Caffeine containing substances including chocolate, coffee, tea Multivitamins, zinc and magnesium Proton pump inhibitors, H2 receptor antagonists Tetracycline Thyroxine Iron inhibits medication absorption Antibiotics (tetracycline) Methyldopa Dolutegravir Quinolones Food or medications that may be used in pregnancy that inhibit iron absorption, or whose action may be inhibited by iron
  • 31. Parenteral Iron Therapy • Intramuscular (IM) Iron • The Ministry of Health and Family Welfare guidelines : • Recommend IM iron following a test dose as a cost-effective treatment for moderate anemia in pregnancy Risks - Inconvenience of painful injection, Dark discoloration of the skin, and The risk of myalgias, arthritis, hypersensitivity, lymphadenopathy Increased risk of development of sarcoma at the site of injection in treated animals Low molecular weight iron dextran is the only preparation which can be recommended for intra muscular use in primary care settings with a Z technique if resuscitation facilities are available
  • 32. Intravenous iron One of the previous disadvantage of IV iron was the requirement of multiple infusions. But now iron-isomaltoside and iron carboxymaltose which allow larger infusion doses of elemental iron to be administered over a short period of time Advantages: • Complete bioavailability with • Fewer GI side effects and • Faster recovery of hb than oral iron. Disadvantages: • The increased risk of oxidant damage, • Increased cost and • Small but finite risk of hypersensitivity reaction limit the widespread use of IV iron
  • 33. Precautions for IV Iron • Parenteral iron should always be administered once ID is confirmed using serum ferritin or other specific investigations, • An informed consent at a center where resuscitation facilities are available. • Vitals should be checked periodically during and at the end of infusion by a physician, nurse or trained mid wife. • A test dose is required only for LMW iron Dextran while other parenteral iron preparations do not require test dosing. • Patient should be explained about the transient side effects of IV iron supplementation include nausea, vomiting, pruritus, headache, and flushing; • Myalgia, arthralgia, and back and chest pain that usually resolve within 48 h of infusion • Ganzoni's equation calculating the dose of par enteral iron in pregnancy is : • Required iron dose[mg] = [2.4×[target hb−actual hb] ×pre – pregnancy weight [kg]] +1000mg for replenishment of stores
  • 34. 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 Indications and contraindications of using IV iron in pregnancy
  • 35. Assessing Response to iron Increase in reticulocyte Hb content (CHr) is the earliest marker of response as early as 3 days. It requires validation in pregnancy and is not widely available currently A rise in hemoglobin by 1 g/dl is expected at the end of 2 weeks and by 2 g/dl by the end of 4 weeks in the absence of other micronutrient deficiencies and ongoing blood loss for patients on oral iron A suboptimal rise is an indication for checking compliance, reconfirmation of diagnosis and consideration for parenteral iron therapy. Once the Hb is in normal range, 100–200 mg/day of iron should continue for at least 3 months and at least 6 weeks postpartum to replenish the stores and 60– 100 mg/d oral iron should continue for at least 3–6 months postpartum
  • 36. Postpartum Anemia Associated with poor quality of life (QOL) and increased rates of depression in women Routine postpartum prophylaxis by WHO recommended doses of 60 mg/d for three months or mohfw doses of 100 mg/d to non-anemic women for 6 months has been shown to be cost effective in decreasing the rates of anemia in our country. It should be reinforced at the time of discharge from health care facility to the lactating mother Hemoglobin should be checked in all women where estimated blood loss is > 500 ml within 48 h of delivery or in women known to have antepartum anemia or having symptoms of anemia . While mildly symptomatic women can be treated with therapeutic oral iron at the dose of 100– 200 mg/d for next 3 months, iv iron can be considered in moderate anemia In case of severe anemia or evidence of hemodynamic comprise patients should receive transfusion prior to discharge from health facility. Wherever feasible, a follow up CBC with serum ferritin should be considered before discontinuation of iron therapy at 3 to 6 months.
  • 37. Role of Erythropoietin • Recombinant human erythropoietin (RhuEPO) has been shown to be safe and effective for the rapid correction of severe peripartum anemia in conjunction with IV iron, particularly in cases with antepartum and postpartum hemorrhage and patients with rare blood groups. • Insufficient evidence for routine use of EPO in pregnancy except in cases with renal disease • Erythropoietin 100-200U/Kg 3times a week until normalization of the red cell and then once a weekly to maintain haemoglobin of approximately 12g/dl.
  • 38. Role of Transfusion • Transfusion in pregnancy carries additional risks :  RBC allo-immunization,  volume overload and  fetal hemolytic disease.  The current AABB and the RCOG guidelines suggest a threshold of Hb < 7 g/dl for transfusion and a threshold of < 8 g/dl in patients with pre-existing cardiovascular disease • The decision of transfusion should be individualized depending on available alternatives of oral and parenteral iron, present and future risk of hemorrhage, comorbidities like DIC, thrombocytopenia, acuteness of fall in Hb and cardiovascular status. • Partial exchange transfusion has not been shown to be superior to transfusion under diuretic cover for patients who present with severe anemia and congestive cardiac failure at term
  • 39. Indications of blood transfusion in pregnancy with IDA Antepartum period Intrapartum period Post partum period 1. Pregnancy < 36 weeks a. Hb < 4 g/dL with or without signs of cardiac failure or hypoxia b. 5–7 g/dL with presence of impending heart failure,hemodynamic instability or acute 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 a. Hb < 7 g/dL[in labor] [Decision of blood transfusion depends on medical history or symptoms] b. Severe anemia with decompensation or acute hemorrhage with decompensation a. Anemia with signs of shock/acute hemorrhage with signs of hemodynamic instability b. Hb < 7gm %:Decision of transfusion depends on medical history or symptoms
  • 40. Management of Labor in Patients with Anemia Heavier blood loss –  Increasing use of regional anaesthesia,  Use of upright position during delivery,  Manual removal of placenta and episiotomy • All patients with anemia should preferably undergo delivery where facility of blood transfusion and intra venous access are available. • Cross matched blood units should be kept reserved in patients with moderate to severe anemia undergoing delivery. • In all anemic patients with pregnancy active management of third stage of labor with the use of syntocin or misoprostol is effective in reducing the blood loss and should be practiced
  • 41. Role of Deworming • WHO recommends routine deworming using single dose Albendazole (400 mg) or mebendazole (500 mg) in all pregnant patients after first trimester in areas where both baseline prevalence of hookworm/Trichuris Trichura infection is > 20% and prevalence of anemia in pregnant women is > 40% and is therefore applicable to India. • Infected women in non endemic areas should receive anti- helmenthic treatment on a case to case basis. The safety of anti-helmenthic agents in pregnancy have not been unequivocally established however deworming is advocated in regions where benefits outweigh the risks
  • 42.
  • 43. Treatment of anaemia from folate deficiency Folic acid 5mg daily for 4 months and is usually given throughout pregnancy. Vitamin B12 deficiency is rare in pregnancy and is treated with intramuscular injections of hydroxocobalamin 1000ug . Initial doses are 6 injections over 2-3 weeks then 100ug every 3 months
  • 44. Other Treatment • Treatment of malaria with artemisin combination therapy, • Bacterial infections with appropriate antibiotics, • Hookworm infestation with mebendazole or albendazole and • Use of highly active antiretroviral therapy according to treatment guidelines in HIV infection. • Other co-morbidities e.G. Diabetes, hypertension should also be managed.
  • 45. Conclusions and Future Vision • IDA in pregnancy is readily manageable yet an unmet health demand. • The management strategy is dependent upon the period of gestation and severity of anemia. • Widespread implementation of preventive and therapeutic strategies is still lacking in our country. • Organization of awareness camps, patient group meetings and the use of social media can spread awareness of this public health issue. • “National Anemia Awareness and Treatment Day” with countrywide participation of health care personnel to target the vulnerable groups specially the pregnant women and teenagers of the country. The day can be used as a platform not only to disseminate knowledge regarding the consequences of anemia on feto-maternal and adolescent health but also to deliver cheap and easy treatment options available for the same.