Anemia in Pregnancy

Definition & Diagnosis

• Mild: 10–10.9 g/dL
• Moderate: 7–9.9 g/dL
• Severe: < 7 g/dL (transfusion threshold typically < 7 g/dL antepartum; < 8 g/dL postpartum)

Physiologic Changes Underlying "Dilutional Anemia"

• Blood volume increases ~40–50% (maximum at ~34 weeks)
• Plasma volume increases ~47%
• RBC mass increases only ~17% (reaches maximum at term)
• This disparity causes physiologic (dilutional) anemia — normocytic, with Hb > 11 g/dL in uncomplicated pregnancy; MCV and MCHC remain unchanged
• Hb nadir typically at 26–28 weeks
• Paradoxically, Hb 13–15 g/dL in pregnancy may reflect inadequate plasma expansion and is associated with low birthweight and preterm birth

Causes of Anemia in Pregnancy

1. Iron Deficiency Anemia (IDA) — Most Common

• Prevalence: iron deficiency in ~18% of US pregnancies; frank IDA in ~5%
• Total iron requirement for a singleton pregnancy: ~1130 mg (range 580–1340 mg)

• Pregnancy demands exceed the iron saved by 9 months of amenorrhea
• ~2/3 of healthy women have minimal bone marrow iron stores before pregnancy
• Iron deficiency progresses through 3 stages:
  1. Prelatent — reduced marrow stores; ↓ serum ferritin; Hb normal
  2. Latent — ↓ serum iron, ↑ TIBC, ↓ % saturation; Hb still normal
  3. Overt IDA — ↓ Hb, ↓ MCV; microcytic hypochromic picture

2. Folate Deficiency — Second Most Common

• Folate requirements increase 5–10 fold in pregnancy
• Risk factors: multiple gestation, short interpregnancy intervals, hyperemesis, malabsorption, alcoholism, antiepileptic drugs (methotrexate, phenytoin, trimethoprim), diet lacking green leafy vegetables
• Causes megaloblastic anemia; also linked to neural tube defects, placental abruption, preterm birth, preeclampsia
• Distinguish from B12 deficiency: serum folate normalizes rapidly with diet; RBC folate better reflects stores; check methylmalonic acid (MMA) if B12 suspected

3. Vitamin B12 Deficiency

• Less common; seen with strict vegetarian/vegan diets, pernicious anemia, gastric surgery
• Megaloblastic picture; elevated MMA and homocysteine
• Anti-intrinsic factor antibodies specific for pernicious anemia (but only 60% sensitive)

4. Hemoglobinopathies

• Sixfold increased risk of maternal death vs controls
• Complications: more frequent vaso-occlusive crises, VTE (1.7–10× more frequent), preeclampsia, preterm labor, PROM, cesarean delivery, placental infarction
• Fetal effects: SGA, low birthweight, increased perinatal mortality
• Treatment: supportive; hydroxyurea contraindicated (teratogenic); NSAIDs avoided after 30 weeks; regional anesthesia preferred over GA; supplemental iron controversial (risk of iron overload); exchange transfusion may be needed for severe crises
• Prophylactic transfusion: controversial in SCD

• Alpha-thalassemia trait: microcytosis, normal/high RBC count, normal ferritin — distinguish from IDA
• Beta-thalassemia major: requires transfusion support; high-risk pregnancy

5. Aplastic Anemia

• Pancytopenia + hypocellular bone marrow; immune-mediated attack on hematopoietic stem cells
• Pregnancy-associated aplastic anemia may remit after delivery, but diagnosis is uncertain
• Goals: Hb > 8 g/dL, platelets > 20 × 10⁹/L; bone marrow transplant not feasible in pregnancy; immunosuppression (antithymocyte globulin, cyclosporine) used
• Complications: postpartum hemorrhage, abruption, preeclampsia, preterm delivery, fetal demise (especially with severe thrombocytopenia)
• Requires multidisciplinary team (MFM + hematology + anesthesia)

6. Other Causes

• Hemolytic anemias: autoimmune (direct Coombs +), microangiopathic (TTP/HUS/HELLP), PNH, G6PD deficiency
• Anemia of chronic disease/inflammation
• Renal anemia

Laboratory Evaluation

• Microcytic (↓ MCV): IDA, thalassemia, sideroblastic anemia → check ferritin, serum iron, TIBC, Hb HPLC
• Normocytic: dilutional anemia, early IDA, hemolytic anemia, aplastic anemia, anemia of chronic disease
• Macrocytic (↑ MCV): folate or B12 deficiency, hypothyroidism → check serum/RBC folate, B12, MMA

Maternal and Fetal Consequences

Management

Iron Deficiency Anemia

• First-line for mild IDA (Hb 9–10.5 g/dL): non-enteric-coated ferrous iron (ferrous sulfate, fumarate, or gluconate)
• ACOG/WHO recommend ≥ 30 mg elemental ferrous iron daily for all pregnant women
• Single daily dose is as effective as multiple doses and reduces GI side effects (nausea, constipation, GERD — already heightened in pregnancy)
• Intermittent dosing (2–3×/week) provides similar maternal and fetal benefits with fewer side effects — 2024 Cochrane meta-analysis PMID 39145520 supports this approach

• Not used in the first trimester
• Treatment of choice for:
  • All IDA in the third trimester
  • Severe IDA (Hb < 9 g/dL) in the second trimester
  • Oral iron intolerance or non-compliance
  • Malabsorption syndromes
• Options: ferric carboxymaltose, iron sucrose, low-molecular-weight iron dextran
• Recombinant erythropoietin: limited role; a 2025 systematic review (PMID 39087437) found it is sometimes used for IDA unresponsive to iron alone but evidence is limited

• Reserved for Hb < 7 g/dL antepartum or Hb < 8 g/dL postpartum, or hemodynamic compromise

Folate Deficiency

• All women: 0.4 mg folic acid daily preconception and throughout pregnancy
• Known folate deficiency: 1.0 mg/day
• High-risk (prior NTD pregnancy): 4 mg/day starting 1 month preconception through 12 weeks GA, continued throughout pregnancy

Vitamin B12 Deficiency

• Oral or IM cyanocobalamin; identify and treat underlying cause

Sickle Cell Disease

• Multidisciplinary care; avoid hydroxyurea; prophylactic antibiotics for asplenia; folic acid supplementation; pain management (avoid NSAIDs > 30 weeks); exchange transfusion for severe crises; regional anesthesia

Screening Recommendations

• First prenatal visit: CBC (all women)
• 26–28 weeks: repeat CBC (screen for late IDA and dilutional anemia)
• Ferritin should be checked if Hb < 11 g/dL or risk factors present
• Hemoglobin electrophoresis (HPLC): screen for hemoglobinopathies in at-risk populations

Recent Evidence (2024–2026)