Why does physiologic anemia of pregnancy occur?

Why Physiologic Anemia Occurs in Pregnancy

Physiologic anemia of pregnancy occurs because plasma volume expands by approximately 40-50% (about 1250 mL) while red blood cell mass increases by only 20-30% (250-450 mL), creating a dilutional effect called hemodilution that lowers hemoglobin concentration without representing true pathologic anemia. 1, 2

Mechanism of Hemodilution

The disproportionate expansion of blood components is the fundamental cause:

• Plasma volume increases dramatically by 1250 mL during pregnancy, representing a 40-50% expansion from baseline 1, 2
• Red cell mass increases modestly by only 250-450 mL, representing just a 20-30% increase 1, 2
• This mismatch creates a dilutional reduction in hemoglobin concentration rather than true anemia, which is why it's termed "physiologic" 2, 3

Timeline of Hemoglobin Changes

The hemodilution follows a predictable pattern throughout pregnancy:

• First trimester (weeks 1-12): Hemoglobin begins declining within the first 8-12 weeks as plasma expansion starts 2
• Second trimester (weeks 13-27): The nadir (lowest point) occurs around 24-28 weeks gestation when hemodilution peaks 2
• Third trimester (weeks 28-40): Hemoglobin gradually rises toward pre-pregnancy levels in women taking iron supplements, but remains low without supplementation 1, 2
• Peak plasma volume occurs at 34-36 weeks gestation 2

Trimester-Specific Hemoglobin Thresholds

Because of this physiologic process, anemia definitions vary by trimester:

• First trimester: Hemoglobin < 11.0 g/dL indicates anemia 2, 4
• Second trimester: Hemoglobin < 10.5 g/dL indicates anemia (lower threshold reflects maximal hemodilution) 2, 4
• Third trimester: Hemoglobin < 11.0 g/dL indicates anemia 2, 4

Physiologic Purpose

This hemodynamic adaptation serves critical functions:

• Prepares for expected blood loss at delivery by increasing total blood volume 3
• Reduces blood viscosity to improve placental perfusion 5
• Supports fetal growth by optimizing oxygen delivery despite lower hemoglobin concentration 5

Critical Distinction: Physiologic vs. Pathologic Anemia

A common pitfall is confusing physiologic hemodilution with iron deficiency anemia:

• Physiologic anemia is the expected dilutional effect described above 1, 2
• Iron deficiency anemia is the most common pathologic cause, accounting for 75% of all pregnancy anemias and affecting 18.6% of pregnant women overall 1, 4, 3
• Iron deficiency prevalence increases from 6.9% in first trimester to 29.5% in third trimester due to increased fetal iron demands 4

Warning Sign: Inadequate Plasma Expansion

Paradoxically, hemoglobin > 14.6 g/dL (or hematocrit > 45%) in early pregnancy indicates poor plasma volume expansion and is associated with worse outcomes:

• Increased risk of stillbirth, maternal hypertension, fetal growth restriction, and preterm delivery 2
• Women with hematocrit ≥ 43% at 26-30 weeks have more than twofold increased risk for preterm delivery and fourfold increased risk for fetal growth restriction 2

Clinical Implications

Despite being "physiologic," this hemodilution requires monitoring and often supplementation:

• All pregnant women should receive 30 mg elemental iron daily starting at the first prenatal visit for primary prevention 1, 4
• Screen with complete blood count at the first prenatal visit and again at 24-28 weeks 2, 4
• When anemia is confirmed, increase to 60-120 mg elemental iron daily and recheck hemoglobin after 4 weeks, expecting an increase of ≥1 g/dL 1, 4