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Anaemia in Pregnancy

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1. Definition & Incidence

• WHO definition: Hb < 11 g/dL OR haematocrit < 32% in pregnancy
• Hb < 10 g/dL at any point = anaemia (WHO 1993, CDC 1990)
• Hb ≤ 9 g/dL = requires detailed investigation + treatment
• Incidence: 40-80% in tropics vs 10-20% in developed countries
• Contributes to ~20% of maternal deaths in developing countries

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2. Classification

Physiological

• Relative fall due to plasma volume expansion (↑40-50%) > RBC volume expansion (↑20%)
• Normocytic normochromic; returns to normal by 6 weeks postpartum

Pathological

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3. Grading of Anaemia (WHO 2011)

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4. Physiological Anaemia - Criteria

1. Hb ≥ 10 g%
2. RBC ≥ 3.2 million/mm³
3. PCV ≥ 32%
4. Peripheral smear: normal RBC morphology with central pallor

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5. Normal Blood Values in Pregnancy

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6. Causes of Increased Prevalence in Tropics

Before Pregnancy

• Faulty diet - carbohydrate-rich; phytates/phosphates block iron absorption
• Faulty absorption - intestinal infestation → intestinal hurry; hypochlorhydria
• Excess iron loss - sweat (15 mg/month), hookworm (0.5-2 mg iron/day), menorrhagia, malaria, piles

During Pregnancy

• Increased iron demand (pregnancy doubles requirement)
• Diminished intake - anorexia, vomiting, poverty
• Diminished absorption - antacids, H₂ blockers, PPIs reduce absorption
• Disturbed metabolism - infections suppress erythropoiesis
• Pre-existing anaemia at conception
• Multiple/twin pregnancy, rapidly recurring pregnancy, HMB (fibroids)

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7. Iron Deficiency Anaemia

Clinical Features

• Often asymptomatic (detected incidentally)
• Symptoms: lassitude, fatigue, anorexia, indigestion, palpitations, dyspnoea, giddiness, leg swelling
• Signs: pallor, atrophic glossitis, stomatitis, angular cheilitis, koilonychia, soft systolic murmur, tachycardia, cardiac enlargement, basal crepitations

Investigations - Blood Values in Iron Deficiency

• Peripheral smear: microcytic hypochromic cells, anisocytosis, poikilocytosis
• Bone marrow: normoblastic; absence of haemosiderin granules (Prussian blue stain)

Differential Diagnosis of Hypochromic Anaemia

1. Infection
2. Nephritis / pre-eclampsia
3. Haemoglobinopathies

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8. Complications of Anaemia in Pregnancy

During Pregnancy

• Pre-eclampsia (related to malnutrition/hypoproteinaemia)
• Intercurrent infections (bone marrow depression)
• Cardiac failure at 30-32 weeks
• Preterm labour

During Labour

• Uterine inertia
• PPH - even minimal blood loss is catastrophic
• Cardiac failure (sudden circulatory overload after delivery)
• Shock (even minor trauma)

Puerperium

• Puerperal sepsis
• Subinvolution
• Poor lactation
• Puerperal venous thrombosis
• Pulmonary embolism
• Poor wound healing

Risk Periods (sudden death risk)

1. ~30-32 weeks gestation
2. During labour
3. Immediately post-delivery
4. 7-10 days postpartum (cardiac failure / PE)

Fetal Effects

• Iron transfer to fetus is unaffected by maternal iron deficiency - neonate NOT anaemic at birth
• ↑ Low birth weight
• Intrauterine death (severe maternal anoxaemia)
• ↑ Perinatal loss
• Anaemia in infancy (reduced iron stores)

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9. Treatment of Iron Deficiency Anaemia

Prophylaxis

• Birth spacing ≥ 2 years
• Supplementary iron: Ferrous sulphate 200 mg (60 mg elemental iron) + Folic acid 1 mg daily - start after nausea of pregnancy resolves
• Avoid tea within 1 hour of iron tablet
• Diet rich in iron: liver, meat, egg, green vegetables, jaggery, whole wheat
• Treat hookworm, malaria, piles, UTI
• Hb estimation: first ANC visit, 30th week, 36th week

Curative - Oral Iron Therapy

• Dose: Fersolate 300 mg (60 mg elemental iron) TDS, 1 hour before meals
• Max: 6 tablets/day (step up gradually over 3-4 days)
• Continue until blood picture normalises, then maintenance 1 tablet/day for 100 days post-delivery
• Expected rise: 2 g/dL every 3-4 weeks

1. Wrong typing of anaemia
2. Defective absorption (GI disorders)
3. Non-compliance
4. Concurrent blood loss (hookworm, piles)
5. Erythropoiesis suppressed by infection
6. Co-existent folate deficiency

• Intolerance
• Severe anaemia in advanced pregnancy

Parenteral Iron Therapy

• Contraindication/intolerance to oral iron
• Non-cooperative patient
• First seen in last 8-10 weeks with severe anaemia

1. IV - Total Dose Infusion (TDI) or repeated injections
2. IM - daily/alternate days

• Iron sucrose is safest (ACOG 2008) - 100 mg/dose daily × 10 days
• Sodium ferric gluconate: 125 mg/dose × 8 doses
• TDI advantages: single sitting, early discharge, less costly
• Expected rise: 0.7-1 g/dL/week
• TDI limitation: max Hb response at 4-9 weeks; unsuitable if < 4 weeks to delivery

• Iron dextran (Imferon) 50 mg/mL; 2 mL daily/alternate days; 2-inch needle, upper outer gluteal quadrant
• Drawbacks: painful, abscess risk, skin discolouration

Blood Transfusion

• Correct anaemia from blood loss / combat PPH
• Severe anaemia seen after 36 weeks
• Refractory anaemia

• Cardiac failure from severe anaemia
• Pre-surgery severe anaemia
• PCV < 13% near term

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10. Management During Labour

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11. Megaloblastic Anaemia

• Deranged red cell maturation → megaloblasts due to impaired DNA synthesis
• Almost always due to folic acid deficiency in pregnancy (Vit B12 deficiency is rare)
• Vit B12 daily requirement: 2 µg (non-pregnant), 3 µg (pregnant) - met by any diet with animal products
• Folic acid daily requirement: 200 µg (non-pregnant), 400 µg (pregnant)

Causes of Folic Acid Deficiency

• Inadequate intake (nausea, vomiting, poor diet)
• Increased demand (multiple pregnancy, growing fetus)
• Diminished absorption (intestinal malabsorption)
• Abnormal demand (infections, haemolytic states, chronic malaria)
• Failure of utilisation (anticonvulsants, infection)
• Diminished storage (liver disease, Vit C deficiency)

Causes of Vit B12 Deficiency

Clinical Features

• Insidious onset; first revealed in last trimester or early puerperium
• Anorexia, protracted vomiting, occasional diarrhoea, unexplained fever
• Pallor, glossitis, haemorrhagic patches, hepatosplenomegaly, features of pre-eclampsia (2.5× increased)

Haematological Diagnosis (≥ 2 features required)

• Hypersegmented neutrophils (≥ 5 lobes)
• Macrocytosis + anisocytosis
• Giant polymorphs
• Megaloblasts
• Howell-Jolly bodies
• MCV > 100 µ³; MCH > 33 pg; MCHC normal
• Associated leukopenia + thrombocytopenia
• Serum iron normal/high; TIBC low
• RBC folate < 3 ng/mL; Serum Vit B12 < 90 pg/mL
• Bone marrow: megaloblastic erythropoiesis

Differentiating Folate vs B12 Deficiency

Complications (special to megaloblastic anaemia)

Treatment

• Prophylaxis: 400 µg folic acid daily for all women of reproductive age; 4 mg daily in high-risk (multiple pregnancy, anticonvulsants, haemoglobinopathy)
• Neural tube defect history: 4 mg/day from 1 month before conception to 12 weeks
• Curative: Folic acid 4 mg orally daily × at least 4 weeks post-delivery
• Response in 7-10 days (sense of wellbeing, reticulocytosis, rising Hb)
• Never give folic acid without supplemental iron
• Add IM Vit B12 100 µg daily/alternate days if response to folate alone inadequate
• Ascorbic acid 100 mg TDS enhances folic acid → folinic acid conversion

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12. Dimorphic Anaemia

• Most common type in tropics
• Combined deficiency of iron + folic acid (or Vit B12)
• Blood picture: macrocytic/normocytic + hypochromic/normochromic
• Bone marrow: predominantly megaloblastic
• Treatment: both iron + folic acid in therapeutic doses

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13. Aplastic Anaemia

• Rare in pregnancy; marked decrease in marrow stem cells
• Aetiology: immunological or autosomal recessive; ~30% improve after termination
• Complications: haemorrhage + infection
• Diagnosis: anaemia + leukopenia + thrombocytopenia; bone marrow markedly hypocellular
• Management: repeated transfusions (keep haematocrit > 20%); granulocyte/platelet transfusions; glucocorticoids; bone marrow/stem cell transplant in severe cases; vaginal delivery preferred

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14. Haemoglobinopathies

Sickle Cell Disease

• Point mutation: valine substitutes glutamic acid at position 6 of β-chain
• Sickle cells lifespan: 5-10 days (vs normal 120 days)
• Sickling precipitated by: infection, acidosis, dehydration, hypoxia, cold

• Haemolytic crisis: haemolysis + anaemia + jaundice + leucocytosis + fever
• Painful (vaso-occlusive) crisis: capillary thrombosis → infarction of bones, kidneys, liver, lungs, CNS

• Folic acid 1 mg/day prophylactically
• Iron supplementation only in proven iron deficiency
• Prophylactic/exchange transfusion: keep Hct > 25%, HbA > 20%, HbS < 50%
• Hydroxyurea (stop ≥ 3 months before conception - teratogenic)
• Penicillin prophylaxis (at risk for meningococcus, pneumococcus, H. influenzae)
• Avoid unpressurised air travel
• Epidural anaesthesia preferred; continuous O₂; adequate hydration
• Vaginal delivery preferred; CS only for obstetric indication
• LMWH thromboprophylaxis throughout pregnancy and puerperium

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Thalassaemia Syndromes

• Low MCV + MCH, normal MCHC
• Serum iron + TIBC normal/elevated
• HbA₂ > 3.5% on electrophoresis
• Serum bilirubin mildly raised (2-3 mg%)

• Thalassaemia major: IV/oral iron contraindicated (iron overload); monitor cardiac/liver/thyroid/parathyroid; folate supplementation; CS often needed (small pelvis)
• Thalassaemia minor: oral iron only if lab-confirmed iron deficiency; folate supplementation; blood transfusion rarely needed
• Iron chelation with desferrioxamine for iron overload

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15. Key Points to Remember

• Serum ferritin = single best test for iron deficiency anaemia
• Hb should rise 2 g/dL every 3-4 weeks on oral iron; 0.7-1 g/dL/week on parenteral iron
• Most serious complications: pre-eclampsia, cardiac failure, PPH, sepsis
• Low MCV without iron deficiency → screen for thalassaemia (Hb electrophoresis)
• No response to iron + no reticulocytosis → screen for folate deficiency
• Folic acid alone must always be supplemented with iron
• 75% of anaemia in pregnancy is iron deficiency
• Neonatal iron stores are preserved even in severely anaemic mothers
• Iron sucrose = safest parenteral preparation (ACOG 2008)

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