Anemia During Pregnancy

Definition

• Hemoglobin (Hb) < 11 g/dL in the 1st and 3rd trimesters
• Hb < 10.5 g/dL in the 2nd trimester (some sources use < 10 g/dL)

1. Physiologic (Dilutional) Anemia of Pregnancy

• Starting around week 6-7, blood volume increases by ~40-50% by 34 weeks, primarily driven by a 47% rise in plasma volume
• Red cell mass rises by only 17%, peaking at term
• This disproportionate plasma expansion causes hemodilution, with Hb nadir between weeks 26-28
• MCV and MCHC remain unchanged in pure dilutional anemia - serial monitoring of these indices helps distinguish it from progressive iron deficiency anemia (IDA), where they fall progressively

Hematologic changes during pregnancy - note plasma volume rises much faster than RBC volume, causing a fall in hematocrit. (From Creasy & Resnik's Maternal-Fetal Medicine)

Gravid patients with hemoglobin values of 13-15 g/dL may actually have inadequate plasma volume expansion, which is linked to low birthweight and preterm birth.

2. Causes of Pathologic Anemia in Pregnancy

3. Iron Deficiency Anemia (IDA)

Pathophysiology

Risks of IDA

• Mild-moderate anemia: higher risk of preterm birth, low birth weight
• Severe anemia (Hb < 6-7 g/dL): increased fetal mortality, abnormal fetal oxygenation, premature rupture of membranes, gestational hypertension, reduced amniotic fluid

Diagnosis

• Ferritin cutoff of 30 ng/mL = 92% sensitivity, 98% specificity for IDA in pregnancy
• Note: ferritin is an acute-phase reactant and may be falsely normal in inflammation
• MCV and TIBC are less sensitive/specific than ferritin
• Measuring Hb alone is inadequate to screen for iron deficiency (only 6% of women with ferritin < 20 μg/L are also anemic)

Treatment of IDA

• Ferrous sulfate 325 mg 1-3x daily (most common in the US)
• WHO recommends 60 mg elemental iron + folic acid daily; 30 mg may suffice with micronutrients
• A single daily dose is as effective as multiple doses and reduces GERD risk
• Coadministration with 500 mg ascorbic acid enhances absorption
• Reticulocytosis expected within 7-10 days; Hb can rise ~1 g/dL/week in severe cases
• Continue iron for 6 months after resolution to replenish stores
• Intermittent dosing (2-3x/week) provides equivalent benefit with fewer GI side effects

• Contraindicated in the 1st trimester
• Treatment of choice for IDA in the 3rd trimester and severe IDA (Hb < 9 g/dL) in the 2nd trimester
• Available IV preparations: iron sucrose (most used), ferric carboxymaltose, ferric gluconate, low-molecular-weight iron dextran, ferumoxytol, iron isomaltoside
• Dose formula for IV iron sucrose: weight × (target Hb - actual Hb) × 0.24 + 500 mg; target Hb = 11-12 g/dL; max 200 mg/day
• Meta-analyses confirm significantly higher Hb and fewer adverse events with IV vs. oral iron

4. Folate Deficiency Anemia

• Folate requirements increase 5-10 fold during pregnancy
• Results in megaloblastic anemia (macrocytic with hypersegmented neutrophils, oval macrocytes)
• Low folate is strongly linked to neural tube defects, placental abruption, preterm birth, low birth weight, preeclampsia, spontaneous abortion
• Risk factors: multiple gestations, short interpregnancy intervals, hyperemesis gravidarum, malabsorption, alcoholism, antiepileptic drug use, poor diet
• Treatment: folic acid supplementation; 0.8 mg/day is sufficient where food fortification is standard; higher doses required in high-risk patients

5. Vitamin B12 Deficiency

• Less common but should be considered, especially in vegans, those with pernicious anemia, or malabsorption syndromes
• Also causes megaloblastic anemia
• Anti-intrinsic factor (AIF) antibody test if pernicious anemia is suspected

6. Hemoglobinopathies in Pregnancy

• Increased frequency of pain crises during pregnancy
• Elevated risk of VTE and preeclampsia
• Treatment of pain crises same as in non-pregnant patients
• Hydroxyurea is contraindicated (teratogenic)

7. Laboratory Evaluation Summary

8. Prevention / Prophylaxis

• ACOG, WHO, and major health authorities recommend at least 30 mg elemental iron daily throughout pregnancy for all women
• Routine supplementation reduces the risk of IDA at term
• Women with normal Hb and ferritin > 30 mg/dL do not require treatment, but prophylactic supplementation is still widely recommended

Recent Evidence (2024-2026)

• A 2024 Cochrane meta-analysis (PMID 39145520) on daily oral iron supplementation in pregnancy confirms benefit for reducing IDA and low birth weight.
• A 2025 systematic review (PMID 39087437) found recombinant erythropoietin is a viable option for IDA in pregnancy when other treatments fail.