Anemia During

Pregnancy
By: Dr. A. Ettore
Ob/Gyne Resident
Moderator: Dr. Kiflome
Consultant Obstetrician Gynecologist,
Maternal-Fetal Medicine Fellow
AAU, MF, Department of Obstetrics & Gynecology
Introduction:
 WHO – Anemia affects 2 billion (30% of world’s population).
 20%-52% of women are anemic. 0.8 million have severe
anemia.
 Anemia in pregnant women 38.2% globally
 46.3% in Africa & 48.7% in East Asia
 17.2 million in sub-Saharan Africa – 30% of global cases.
 20% of maternal deaths globally & 45% in developing
countries.
Prevalence of anemia in pregnant women
by WHO regions:
60.00%

50.00%

40.00%

30.00%
48.70% 46.30%
20.00% 38.90% 34.90%
24.30% 25.80%
10.00%

0.00%

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Public health significance of Anemia:
Anemia prevalence Public health significance
≥ 40% Severe
20%-39% Moderate
5%-19% Mild
0-4.9% Normal
 In Ethiopia – EDSH 2016:
 23% of women – 15-49 yrs – are anemic:
18%

16%

14%

12%

10%
17%
8%

6%

4%
5%
2%

0% <1%
Mild Anemia Moderate Anemia Severe
Percentage of women age 15-49 years classified as having
anemia, by background characteristics, Ethiopia 2016 - EDHS:
 Institutional-based, cross-sectional study Nov.2012 –
March.2013 Prevalence of Anemia in Pregnant
attending ANC in TASH is 21.3%.
 80.95% mild, 17.86% moderate & 1.19% severe.
 Facility-based, cross-sectional study; prevalence and
associated factors of anemia among pregnant in
Mekelle town is 19.7%
Definition:
 Quantitative or qualitative reduction in Hb or RBC’s or
both resulting reduced oxygen – carrying capacity of blood.
 Reduction in circulating Haemoglobin mass
 < 12g/dl in non-pregnant women
 < 11 g/dl in pregnant women.
 WHO/CDC: Hb < 110 g/L or Hct< 33% in 1st % 3rd Tm ; in
2nd Tm Hb < 105 g/dL or Hct < 32%.
WHO grading of anemia:
Mild Anemia Moderate Anemia Severe
10 – 10.9 mg/dL 7 -9.9 mg/dL < 7 mgl/dL

WHO definition (11mg/dL):

I. Prevalence of anemia in pregnancy – 15%-67%
 Sub-Saharan – 30%-65% & developed countries 25% (high)
II. 3.0%-7.3% of anemia-related maternal death in developing countries (low)
Hematological changes
in pregnancy:
 Augmented erythropoiesis in pregnancy
 Plasma vol. increased by 50% - 6th plateau at 34th wks.
 RBC’s increased by 30% from 10th – term.
 There’s 2-3x increase in erythropoietin level.
 Disproportionate increase in plasma vol. RBCs & Hb during
pregnancy.
Normal values in pregnancy:
Physiologic Anemia:
 Criteria for Physiologic Anemia
 Hb: 10 gm%
 RBC: 3.2 million/mm3
 PCV: 30%
 Peripheral smear showing normal morphology of RBC with
central pallor
Causes of Anemia:
A. Physiological B. Acquired C. Genetic/
Hemoglubinopathies
a. Nutritional deficiency anemia: a. SCD
• Iron deficiency b. Thalassemias.
• Folate deficiency
• Vit. B12 deficiency
b. Infections:
• Malaria & Hookworm
c. Hemorrhage:
• Acute/Chronic blood loss
d. Bone marrow insufficiency:
• Aplastic anemia
e. Renal disease
Morphologic classification:
Microcytic
(MCV < 80 fl)
 I ron Deficiency
 Anemia of Chronic Disease
 Thalassemias
 Hemoglobinopathies
 Sideroblastic Anemia
Normocytic
(MCV 80-100 fl)
 Acute blood loss
 Anemia of chronic disease
 Early iron deficiency
 Hemoglobinopathies
 Primary marrow disorders
 Combined deficiencies
 Increased destruction
 Chronic renal
insufficiency
Macrocytic
(MCV>100 fl)
 Folic acid deficiency
 Vitamin B-12 defficiency
 Liver disease
 drugs abuse
 Hemoglobinopathies
 Metabolic disorders
 Primary marrow disorders
 Increased destruction
Effect of anemia on pregnancy:
a. Maternal:
Antepartum Intrapartum Postpartum
I. PIH/PE i. CCF i. Puerperal sepsis
II. Increased infections ii. Shock ii. Subinvolution
III. CCF iii. Faling lactation
IV. APH iv. Purrperal venous
thrombosis
v. Pulmonary embolism

b. Fetal:
1. ↑ incidence of abortion 6. Cerebral vasodilatation
2. IUGR 7. Stillbirth
3. Prematurity 8. ↑ PMN
4. Decreased AVF 9. ↑ risk of IDA in infancy
5. NRFHBP
Iron deficiency anemia:
 The most common cause of anemia in gravid women,
 75 to 80 % of anemia that occur during pregnancy
 22% maternal deaths and 24% PNM annually around
the world.
 Absolute iron deficiency is defined as ferritin <12 µg/L
with or without iron saturation <20%.
Iron requirement & metabolism during
pregnancy:
 Normal pregnant women body iron content — 3 to 4 g
 500 mg to increase the maternal RBC mass
 300 mg transported to the fetus, and
 200 mg to compensate for the normal (obligatory) daily loss
 2.5 mg/day – early pregnancy
 5.5 mg/dya – 20-32 weeks
 6.8mg/day – after 32 wks
i. Iron loss during pregnancy and delivery 3mg/day – in
280 day = 840 mg
ii. 500 mg of storage iron is required to avoid IDA during
pregnancy
i. Only 20% of pregnant women have 500 mg of storage iron
ii. 40% have 100-500 mg and other 40% have no storage iron.
 Iron transferred from mother to fetus by transferrin on
syncytiotrophoblast – there’s ↑ placental transferrin
receptors during pregnancy.
 Absorption of iron depends on:
a. Amount of iron in diet
b. Bioavailability of iron
c. Physiological requirement
Factors modify iron absorption:
1. Physical state Heme > Fe² > Fe³
2. High gastric pH Vagotomy, pernicious anemia,
H2 receptor blockers
Calcium-based antiacids
3. Intestinal structural disruption Cohn’s disease
Celiac disease
4. Inhibitors Phytates & Tannins
5. Competitors Cobalt, Lead
6. Facilitators Ascorbate, Citrate, amino acids & iron
deficiency
Risk factors for iron deficiency anemia:
1. Nutritional & low iron intake
2. Acute blood loss
3. Nausea &vomiting
4. History of heavy mens
5. High parity
6. Short birth spacing
7. Lack of antenal nutritional education
8. Multple pregnancy
9. Infections
 Parasitic infestation
 Malaria
10. Malabsorption.
Etiology of IDA:
 Inadequate dietary intake   Inadequate GIT absorption
 Poor nutrition  Malabsorption syndromes
 Chronic alcoholism  Certain drugs/foods  
 Decreased consumption of animal  Blood loss
protein and ascorbic acid    Hookworm infestation
 Increased iron demands  Malaria
 Multiparity  Bleeding piles &gums
 Diarrhea, HIV/ AIDS and  Surgery
 UTI  Gastrointestinal bleeding
 Recurrent Infections- Tuberculosis,  Trauma
Amoebiasis , Giardiasis, Roundworm  Dialysis
 other infectious diseases
Clinical signs and symptoms of
iron deficiency:
Diagnosis of anemia in pregnancy:

WHO – (2016) Recommendation:

Investigations for diagnosis of IDA:
1. Haematocrit 7. Serum iron < 50 μgm/dl
2. RBC Indices: 8. TIBC is increased - > 400 μgm/dl
• Low MCV 9. Serum ferritin is < 12 μgm/dl
• Low MCH 10. Serum transferrin saturation<20%
• Low MCHC 11. Red cell Zinc Protoporphyrin
• Low PCV 12. Serum transferrin receptor(TfR) : Increased
3. Peripheral blood 13. Bone marrow examination.
4. Stool examination 14. Reticulocyte hemoglobin conc. : Count of
5. Hb electrophoresis <26pg/ cell
6. X-ray Chest(PA View) 15. LFT, RFT
16. Trial of iron therapy-diagnostic & therapeutic
Basic approach for detection of iron deficiency anemia (IDA)
using correct hemoglobin and ferritin values
Test
Blood smear hypochromia
MCV
Serum iron
Iron binding capacity (IBC)
Iron/IBC (% saturation)
Ferritin
Stool for occult blood
Bone marrow for iron stores
Limitations
Subjectivity
Insensitivity
Markedly lowered by fever or
inflammation
Moderately lowered by fever; increased
by pregnancy
Like serum iron, lowered by fever
Mildly raised by fever or inflammation
Bleeding may be intermittent
Expensive and invasive; iron depletion
does not prove IDA
Prevention of IDA:
 Dietary modification
 Iron supplementation of adolescent & non pregnant female
 Treatment of Hookworm infestation
 Control of malaria
 Iron supplementation in pregnant Women
 Food fortification
 Antenatal care for early recognition
 Optimal birth spacing
Dietary Education:
 Rich in iron - liver, beef, whole-grain breads, cereals, eggs,
dark green vegetables and dried fruit.
 High in folic acid, wheat germ, beans, peanut butter,
oatmeal, mushrooms, collards, broccoli, beef liver and
asparagus.
 High in vitamin C, citrus fruits and fresh, raw vegetables.
Vitamin C makes iron absorption more efficient.
 Take prenatal vitamin and mineral supplements, especially
folic acid.
Prophylaxis of IDA:
 30 - 60 mg of elemental iron and 400 μg (0.4 mg) folic acid is
recommended for pregnant women. – WHO.
Treatment of IDA:
 Depends on:
I. Severity of anemia
II. Gestational age.
Drawback Side effects
a. Intolerance a. Nausea & Vomiting
b. Unpredictable absorption rate. b. Gastric irritation
c. Not suitable for patients with GI diseases c. Constipation
d. Non Compliant patient. d. Abdominal cramp
e. Long time for improvement e. Diarrhea
Effectiveness of Iron
Supplementation:
 Clinical improvement
 laboratory indices
 Reticulocyte count
 Hemoglobin
 Ferritin levels
 Newer measurements:
 Reticulocyte hemoglobin content
 Percent hypochromic RBCs
 Soluble transferrin receptors (sTfR))
Parenteral Iron Therapy:

 Indications:
a. when unable to take iron due to side effects
b. Non compliant
c. Suffers from inflammatory bowel disease
d. Near term
e. With chronic renal disease
A. Intravenous preparation
 Iron dextran (Imferon)
 Iron sucrose
 Sodium ferric gluconate (ferrlecit)
B. Intramuscular preparation
 Iron Sorbitol Citrate in dextrin(Jectofer)
 Iron Dextran (imferon)
Parental cont’ed …
Contraindications Advantages Disadvantages
i. History of anaphylaxis i. Certainty of i. Nausea and Vomiting
to parenteral iron admission. ii. Metallic taste on
therapy ii. Hb rises @1gm/wk. tongue
ii. First trimester of
pregnancy
iii. Active acute/chronic
infection
iv. Chronic liver diseases
IM R0ute:

 Iron Dextran (1ml contains 50mg elemental iron &

1amp=2ml) Dose : 100 mg IM.

Drawbacks: Advantage
1. Painful injection 1. Can be given in primary care set up
2. Skin discoloration 2. Absolute reticulocyte count increases
3. Local abscess in 7 days
4. Allergic reaction 3. Hemoglobin increases within 1-2 wks
5. Fe over load. 4. Whole dose can be given in single
6. Category C drug setting
7. Gluteal sarcoma
8. Test dose needed
I/V Route:

a. Given either:
 Repeated Injections
 Total dose infusion
b. Side effects:
 Anaphylactic reaction.
 Chest pain, rigors, chills, fall in BP, dyspnoea, hemolysis
 Treatment:
 Stop infusion.
 Give antihistaminics, corticosteroids & epinephrine.
Total dose infusion TDI:

 Caculation:
 TDI=(Normal Hb - Patients Hb) X Blood Volume (65ml/kg) X3.4
100
 TDI= (Normal Hb – Pt. Hb) X Wt in Kg X 2.21+1000
 TDI=[10 × (target Hb-actual Hb ) × (0.24 × bodyweight )] +0/500
 Management of anemia in pregnancy:
Pregnancy <30 wks Pregnancy 30-36 wks
Pregnancy > 36 wks

IDA FA deficiency

IDA FA deficiency IM IV FA oral Blood transfusion

Oral iron Oral FA

Intolerance or non-compliance

Iron IM Iron IV
Reasons for Failure to Respond:
1. Non compliance
2. Concomitant folate deficiency .
3. Continuous loss of blood through hookworm infestation or bleeding hemorrhoids
4. Co-existing infection .
5. Faulty iron absorption
6. Inaccurate diagnosis
7. Non iron deficiency microcytic anemia:
 Thalassaemia
 Pyridoxine deficiency
 Lead poisoning
 Sideroblastic anemia
Blood transfusion:
A. Decision based on
1. Needs and risk of developing complications of inadequate
oxygenation
2. Both clinical and hematological grounds
B. Indications
1. Severe anemia, especially after 36 weeks
2. Risk of further hemorrhage
3. Associated infections
4. Imminent cardiac compromise
Department of Hematology – (AAU) Recommendations on Blood
Transfusion during Pregnancy:
a. Pregnancy less than 36 wks:
b. Pregnancy 36 wks or more:
c. Elective caesarean section: if there’s history of
 APH
 PPH
 Previous CS
If Hb 5 g/dL, transfuse irrespective of clinical
condition.
If Hb 5-7g/dl transfuse transfuse in presence of:
 Estalished/impending CCF or evidence
hypoxia
 Pneumonia or bacterial infection
 Malaria
 Preexisting heart disease.
If Hb 6mg/dl or less irrespective of clinical
condition
If Hb 6-8mg/dl in presence of clinical coditions
If Hb 8-10, establish patient’s BG & save freshly
taken sample for cross-matching
If Hb < 8mg/dl have 2 units of cross-matched
blood available.
Management during labor:

1. Consideration for delivery in well equipped hospital.

2. Adequate analgesia.
3. Supplemented with oxygen therapy
4. Prophylactic forceps/Vacuum to cut short 2nd stage
5. Decreased blood loss by active management of 3rd stage of
labors.
6. Avoid maternal stress, patient can go into CHF.
7. PPH – should be emergently treated.
Anesthetic considerations:
1. Pre oxygenation is mandatory with 100% O2
2. O2 supplementation should be given in peri and
postoperative periods
3. Blood arrangements prior to surgery
4. Airway maintenance to prevent fall of PO2 due to airway
obstruction
5. Hyperventilation to be avoided to minimize respiratory
alkalosis
6. General/spinal anaesthesia can be given after platelet count
and excluding h/o spontaneous hemorrhage.
Megaloblastic anemia:
 Occurs in 0.2-5%, caused by deficiency of folate & vit.
B12.
 Pthophysiology:
 Folate requirement is 50μg/day in non-pregnant increase to
300-500 μg/day in pregnancy
 Vit. B12 deficiency occurs in Gastrectomy, ileitis, ileal
resection, pernicious anemia & intestinal parasites
Folic acid anemia diagnosis:
a. Hb <10 g/dl
b. ↑ MCV –(> 100fl)
c. Peripheral smear:
 Macrocytosis hypochromia
 Hypersegmented neutrophils
 Neutropenia
 Thromboctopenia
d. Low serum folate - < 3 ng/ml
e. Low RBC folate - < 20 ng/ml
Prevention:
 Women contemplating pregnancy should be advised - WHO:
 0.4 mg/day if there is no family history of neural tube defect
 4 mg/day if she high risk patient
 Education on diet is recommended
 Folate food fortification.
 Treatment:
 Folate 5 mg three times a day
 B 12 deficiency requires vit. B 12, 1 mg IM, weekly for 6 weeks
 Response to folate treatment:
I. Reticulocytosis within 3 days
II. Hematocrit level may rise by 1% daily after 1 week of
treatment.
III. Carries a good prognosis if adequately treated
Hemoglobinopathy:
a. Sickle cell disease:
 Sickle cell anemia
 Sickle cell beta thalassemia
 Hb –SC disease
b. Thalassemia:
 Alpha thalassemia
 Beta thalassemia – major & minor.
Sickle cell anemia:
 Valine substitute for glutamic acid in beta chain.
 Common variants are:
 SS ( sickle cell anemia)
 SA ( sickle cell trial)
Hb SS Hb SA
Cell triat Homozygous Heterozygous
Hb S 70-90%, rest Hb F 10-40%, 40-60% HbA
Hb( g/dl) 6-9 13-15
Life expectancy 30 yrs Normal
Propensity for sickling ++++ ++ ( O2 < 40%)
Maternal and fetal risks:
Clinical manifestations of sickle cell anemia:
Growth and development Abdominal involvement
1. Retarded growth 1. Painful vaso-occlusive episodes
2. Skeletal changes 2. Hepatomegaly
3. Decreased life span 3. Hepatitis
Sickle cell crisis 4. Cholecystitis
1. Painful vaso-occlusive episodes: bones, 5. Splenic infarction
abdomen, chest, and back Bone and joint changes
Cardiovascular manifestations of hyperdynamic 1. Bone marrow infarction
circulation 2. Osteomyelitis: Salmonella
1. Cardiomegaly 3. Arthritis
2. Systolic murmurs Genitourinary signs
3. Failure 1. Hyposthenuria
Pulmonary signs 2. Hematuria
1. Infection: pneumococcus, Mycoplasma, 3. Pyelonephritis
Haemophilus, Salmonella Neurologic manifestations
2. Vascular occlusion 1. Vascular occlusion
2. Convulsions
3. Hemorrhage
4. Visual disturbances
Ocular manifestations
1. Conjunctival vessel changes
2. Vitreous hemorrhage
Diagnosis:
 Hb solubility test-specific, cheap, rapid and simple.
 Sickling test
 Hb electrophoresis,
General management of sickle cell
during pregnancy:
A. Preconception: B. Booking
I. Discuss maternal/fetal risk I. Early booking & planned schedule b/n
II. Paternal screening obstetrician & hematologist
III. Folic acid supplementation II. CBC, U/E, Forritin & folate
IV. Review medications III. Partner screening
V. Thromboprophylaxis IV. Folic acid
V. h/o previous pregnancy, crisis & transfusion
VI. Review of medications
VII. Signs & symptoms of chest
syndrome/infection – early report
VIII.Echocardiography for Lt vent. Function &
pulmonary HTN
IX. Obstetric ultrasound for GA, viability &
growth monitoring
Labor & delivery:
A. Intrapartum
 To achieve spontaneous vaginal delivery
 CBC, BG & x-matched blood & U/E
 Keep warm, hydrated & oxygenated
 Continuous puls oxymetry
 Continuous FHR monitoring
 Avoid prolonged labor/ROM
 Epidural analgesic
 If operative – spinal anesthesia
 thromboprophylaxis
B. Postpartum
 Keep hydrated & oxygenated
 Vital signs every 04 hrs in 1st. 12 hrs
 Watch for signs of painful chest crisis
 Continue thromboprophylaxis
 Low threshold for antibiotics
 Check CBC in day 1
 Early ambulation
 Appropriate contraception
 Ensure postnatal follow-up with
hematologist
Management dilemmas:

a. Delivery:
 Planned induction at 38 wks vs spontaneous labor
 CS if indicated, optimize prenaenthesia:
 Hydration
 Oxygenation
 Blood transfusion
 Post op chest physiotherapy
b. Hydroxycarbamide:
 Animal studies – associate with hydrocephalus, lack of eye
stocklet & missing lumber verteral bone
 Case series – no evidence of teratogenicity during
pregnancy.
 Male & female – stop 3 moths before pregnancy planning
 Accidental pregnancy – stop drug.
c. Prophylactic transfusion vs indicated:
 Retrospective study of routine transfusion in early pregnancy in
UK:
I. ↓ sicklning complications in 3rd. Tm & puerperium
II. No evidence of growth change or neonatal outcome
 Blood transfusion only indicated in:
I. Hb <6g/dl
II. Anaemia with cardio or respiratory compromise
III. History of severe sickle related complications
IV. Patient already on a chronic transfusion programmes
V. Twin pregnancies
Thalassemia:
 The synthesis of globin chain is partially or completely
suppressed resulting in reduced Hb content in red cells which
then have shortened life span.
 TYPES:
 Alpha thalassaemia.
 Beta thalassaemia: Major & Minor
Diagnosis:
 Globin chain synthesis studies.
 Occasionally mild anaemia (MCV↓, MCH↓, MCHC=)
 May present with severe anemia at 4-6 months
 Splenomegaly, Jaundice.
 Pain from bone infarcts (later in life—ulcers of legs).
 Treatment:
 Transfusions
 folic acid supplementation, iron supplementation when iron deficiency is
diagnosed
 Treat infections early.
Preconception evaluation:

1. Cardiac evaluation & quantification of cardiac iron

2. GTT & optimize glucose if DM
3. Iron chelators
4. Folic acid supplementation
5. Review medication
6. Smoking & alcohol cessation.
Management of thalassemic women during pregnancy:
1. Multidisciplarlinary approach – (Obstetrician, hematologist & cardiologist)
2. Early booking
3. CBC, BG & XMB, RFT, LFT, electrolytes
4. Review medication:
i. Stop ACE inhibitors & biphosphonate
ii. Stop iron chelatos
iii. Continue with folic acid and prophylactic pcrenicillin and
thromboprophylaxis
iv. Vit. D & calcium if BMD decreased
5. Advice against smoking & alcohol consumption
6. Discuss mode of delivery
7. Discuss contraception option post delivery.
 Other RBC disorders:
Glucose-6phosphate dehydrogenase Hereditary spherocytosis:
deficiency:
1. X-linked, 20% in African, Asian & Southern 1. Autosomal dominant
Europe 2. RC membrane defect – spherical
2. Hemolysis in stressful conditions: i. ↑ osmotic fragility
i. Infection ii. ↓ Hb
ii. Drugs iii. Hemolytic anemia
iii. Pregnancy 3. 10% have severe anemia – Hb 6mg/dl
3. Diagnosis: peripheral BF comfirm by G6PD 4. Diagnosis is comfirmed by
quantitation by pectrophotometric assay i. Osmotic fragility test
4. Management: ii. Cytometry
i. Check for hemolysis & precipitating 5. Management:
factors i. Most conservatively
ii. Folic acid ii. In severe anemia, blood transfusion, or
iii. Educate for S/S of hemolysis splenectomy.
iv. Neonate cord blood Hb, bilurobin & G6PD
assay
Summary/Recommendations:
 All pregnant women should be screened for anemia
 Asymptomatic women with anemia need further
evaluation
 Universal supplementation of iron and folic acid
 Nutrition education and family planning
 Blood transfusion only when indicated
 Parental iron rarely needed in indicated circumstances
 Good standard practice during parturition to minimize
blood loss
 Early joint evaluation of women with
hemaglobinopathies by hematologist.
Finally……

WHO IS ETHIOPIAN!
THANKS!
References:
 Hematological Complications in Obstetrics, Pregnancy, and Gynecology,
2006, Edited by Rodger L. Bick (Editor in Chief ) University of Texas
Southwestern Medical Center, Dallas, Texas, USA Eugene Frenkel (Editor)
 The Obstetric Hematology Manual 2010, Edited by Sue Pavord University
Hospitals of Leicester NHS Trust Beverley Hunt Guy’s and St. Thomas’
 Creasy & Resnik’s Maternal – Fetal Medicine 8th edition,
 Willams Obstetrics 24th
 Iron Deficiency Anemia: A Public Health Problem of Global Proportions
Christopher V. Charles University of Guelph, Canada
 Iron Deficiency Anaemia Assessment, Prevention and Control
A guide for programme managers WHO, 2001
 THE GLOBAL PREVALENCE OF ANAEMIA IN 2011 World
Health Organization 2015 edition.
 Anemia in pregnancy, ACOG practice bulletin No. 95, 2008
 Anemia and iron deficiency: effects on pregnancy outcome
Lindsay H Allen Am J Clin Nutr 2000
 WHO recommendations on antenatal care for a positive pregnancy
experience – 2016 edition.
 Demographic and Health Survey 2016 Key Indicators Central Statistical
Agency Addis Ababa, Ethiopia.