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Anemia in Pregnancy — Complete MBBS Study Guide

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1. Definition

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2. Physiologic Anemia of Pregnancy

• Plasma volume expands 40–50% above baseline (peaks at weeks 16–24)
• Red cell mass expands only 15–25%
• Net result: dilutional decrease in Hb — normocytic, normochronic

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3. Classification & Causes

By MCV:

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4. Iron Deficiency Anemia (IDA) — The Most Common

Why IDA is common in pregnancy:

• Fetal and placental iron needs: ~300 mg
• Expansion of maternal red cell mass: ~500 mg
• Basal losses: ~200 mg
• Total iron demand: ~1,000 mg over pregnancy
• Daily iron requirement rises from ~0.8 mg/day (non-pregnant) to 6–7 mg/day (third trimester)

Clinical Features:

• Symptoms: Fatigue, weakness, lightheadedness, exertional dyspnea, palpitations
• Signs: Pallor (conjunctiva, palms, mucous membranes), tachycardia, angular stomatitis, koilonychia (spoon nails), glossitis, brittle nails
• Pica (craving non-food items — ice, clay, starch) is pathognomonic
• Often discovered incidentally on routine CBC

Stages of Iron Deficiency:

1. Iron depletion — Ferritin ↓, iron stores exhausted, no anemia yet
2. Iron-deficient erythropoiesis — Serum iron ↓, TIBC ↑, transferrin saturation ↓, no anemia yet
3. Iron deficiency anemia — Hb ↓, microcytic hypochromic RBCs on smear

Peripheral Blood Smear in IDA vs Normal:

Lab Findings in IDA:

Serum ferritin is the single most accurate lab value for diagnosing IDA in pregnancy. — Rosen's Emergency Medicine

Treatment of IDA:

• Ferrous sulfate 325 mg (60 mg elemental iron) — one tablet once or twice daily
• Take on empty stomach for best absorption; vitamin C enhances absorption
• Side effects: nausea, constipation, dark stools — take with food if needed
• Hemoglobin should rise ~1 g/dL per week with adequate therapy
• Continue therapy for 3 months postpartum to replete stores

• Indications: intolerance to oral iron, non-compliance, malabsorption, severe or late anemia
• Agents: ferric carboxymaltose, iron sucrose, low molecular weight iron dextran
• IV iron replenishes stores faster and more effectively than oral iron
• A 2024 JAMA systematic review for the USPSTF confirmed iron supplementation reduces IDA in pregnancy but ongoing research examines optimal dosing strategies (PMID: 39163033)

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5. Folate Deficiency Anemia (Megaloblastic)

Why common in pregnancy:

• Folate requirements nearly double during pregnancy (from 400 μg to 600–800 μg/day)
• Increased cell proliferation demands more folate for DNA synthesis
• Poor dietary intake, multiple pregnancy, hemolytic states all increase risk

Clinical Features:

• Megaloblastic anemia: macrocytic (MCV > 100), hypersegmented neutrophils
• Glossitis, angular stomatitis, mild jaundice
• No neurological deficits (unlike B12 deficiency)
• Increased risk of neural tube defects in the fetus if deficiency is in early pregnancy

Peripheral Smear in Megaloblastic Anemia:

Lab Findings:

• Hb ↓, MCV ↑ (>100 fL), MCHC normal
• Hypersegmented neutrophils (>5 lobes in >5% of neutrophils)
• Serum folate ↓, RBC folate ↓ (more reliable)
• LDH ↑, indirect bilirubin ↑ (ineffective erythropoiesis)
• Megaloblasts in bone marrow

Treatment:

• Folic acid 5 mg/day orally until recovery, then maintenance
• Prevention (all pregnancies): Folic acid 0.4–0.5 mg/day from at least 4 weeks before conception to 12 weeks gestation → reduces neural tube defect risk by ~70%
• High-risk women (prior NTD, anticonvulsants): 4–5 mg/day

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6. Vitamin B12 Deficiency

• Less common than folate deficiency in pregnancy
• Causes: strict vegetarianism/veganism, pernicious anemia (autoimmune), post-gastric surgery
• Macrocytic anemia + subacute combined degeneration of spinal cord (posterior and lateral column demyelination — neurological feature that distinguishes B12 from folate deficiency)
• Treatment: Hydroxocobalamin or cyanocobalamin IM injections

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7. Sickle Cell Anemia in Pregnancy

• HbSS carries the highest risk — maternal mortality significantly elevated
• Complications:
  • Increased vaso-occlusive crises (due to hyperviscosity, dehydration, infection)
  • Preeclampsia, placental abruption
  • Preterm labor, fetal growth restriction, stillbirth
  • Acute chest syndrome
• Management:
  • Prophylactic folic acid (5 mg/day — higher doses due to hemolysis)
  • Hydration, analgesia for crises
  • Avoid hydroxyurea in pregnancy (teratogenic)
  • Exchange transfusion for severe complications (acute chest, stroke)
  • Serial ultrasound for fetal growth
  • Genetic counseling — partner screening for HbS trait

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8. Thalassemia in Pregnancy

α-Thalassemia:

• α-Thal trait: mild microcytic anemia → must distinguish from IDA (normal ferritin, no response to iron)
• If both partners carry α-thal trait in cis (--/αα) conformation → 25% risk of Hb Bart's → offer prenatal diagnosis

β-Thalassemia:

• β-Thal minor (trait): Mild anemia, microcytic; elevated HbA2 >3.5% on electrophoresis; well tolerated in pregnancy; folic acid supplementation
• β-Thal major (Cooley's anemia): Rarely pregnant without transfusion support; managed with regular transfusions, chelation (avoid deferoxamine in first trimester), and careful monitoring
• β-Thal intermedia: Variable; may worsen in pregnancy; manage as per severity

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9. Aplastic Anemia in Pregnancy

• Rare but life-threatening
• Pancytopenia: anemia + neutropenia + thrombocytopenia
• Most serious complications: hemorrhage and sepsis — leading causes of maternal death in aplastic anemia
• Bone marrow biopsy: hypocellular marrow
• Management:
  • Supportive transfusions (packed RBCs, platelets)
  • Immunosuppression (antithymocyte globulin, cyclosporine)
  • Bone marrow transplantation ideally deferred until after delivery
  • High-dose corticosteroids considered in some cases

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10. Anemia of Chronic Disease / Infection

• Normocytic, normochromic anemia
• Associated with chronic infections (HIV, TB, pyelonephritis), chronic renal disease, chronic liver disease, autoimmune conditions
• Pathophysiology: ↑ hepcidin → ↓ iron release from macrophages → functional iron deficiency
• Distinguish from IDA: ferritin is normal or elevated in ACD
• HIV-associated moderate–severe anemia in pregnancy → workup for tuberculosis (per Rosen's)
• Treatment: treat underlying condition; iron supplementation only if concurrent IDA confirmed

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11. Maternal and Fetal Consequences of Anemia

Maternal Effects:

• Fatigue, impaired work capacity
• Cardiac decompensation (high-output heart failure in severe anemia)
• Increased susceptibility to infection
• Postpartum hemorrhage poorly tolerated
• Peripartum cardiomyopathy risk
• Increased maternal mortality (severe anemia, Hb < 6 g/dL)

Fetal/Neonatal Effects:

• Fetal growth restriction (FGR)
• Preterm birth
• Low birth weight
• Neonatal anemia
• Increased perinatal morbidity and mortality
• Neural tube defects (folate deficiency in first trimester)

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12. Screening and Routine Evaluation

• CBC at booking (first antenatal visit) and again at 28–32 weeks
• WHO and most national guidelines recommend screening all pregnant women
• Additional tests based on CBC morphology (see Table below)

Evaluation Algorithm:

CBC with differential + reticulocyte count
         ↓
  MCV < 80 (Microcytic)      MCV 80-100 (Normocytic)     MCV > 100 (Macrocytic)
         ↓                          ↓                            ↓
Serum ferritin, TIBC,         Reticulocyte count          Serum folate, B12,
serum iron, Hb electrophoresis  ± bone marrow            LDH, PBS
         ↓
Ferritin ↓ → IDA
Ferritin normal + micro → Thalassemia (electrophoresis)
Ferritin ↑ → ACD

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13. Prevention

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14. High-Yield Summary for Exams

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Key Sources

• Creasy & Resnik's Maternal-Fetal Medicine: Principles and Practice, Chapter 55 (Anemia in Pregnancy), pp. 1329–1344
• Goldman-Cecil Medicine, Section on Physiologic Anemia of Pregnancy, p. 1676
• Harrison's Principles of Internal Medicine, 21st ed., pp. 1721, 2889
• Recent USPSTF systematic review on iron supplementation in pregnancy: JAMA 2024 (PMID 39163033)