Timing of Dilutional Anemia in Pregnancy
Dilutional anemia in pregnancy begins during the first trimester, progresses throughout the second trimester, and reaches its nadir (lowest hemoglobin point) at approximately 24-28 weeks gestation in the late second trimester, with hemoglobin levels gradually rising toward pre-pregnancy values in the third trimester if adequate iron supplementation is provided. 1, 2
Physiologic Timeline
First Trimester (Weeks 0-13)
- Plasma volume expansion begins with minimal increase initially 3
- Hemoglobin concentration starts to decrease due to early hemodilution 1, 4
- Some evidence suggests a preliminary fall in red cell mass may occur during this period 3
- Anemia is defined as hemoglobin <11.0 g/dL during this trimester 2, 5
Second Trimester (Weeks 14-27)
- Progressive and dramatic plasma volume expansion occurs, increasing by approximately 1250 mL (nearly 50% above non-pregnant levels) 3
- Hemoglobin concentration continues to decline, reaching its lowest point 1, 4
- The nadir typically occurs around 24-28 weeks gestation 6
- Anemia is defined as hemoglobin <10.5 g/dL during this trimester 1, 2, 5
- Red cell mass increases by only 250 mL without iron supplementation (versus 400-450 mL with supplementation), creating the dilutional effect 3
Third Trimester (Weeks 28-40)
- Maximum plasma volume is reached at approximately 34-36 weeks, after which little further increase occurs 3
- In women taking iron supplements, hemoglobin gradually increases toward pre-pregnancy levels 1, 4
- In women not taking iron supplements, hemoglobin remains low throughout this trimester 1
- Anemia is defined as hemoglobin <11.0 g/dL during this trimester 1, 2, 5
Mechanism of Dilutional Anemia
The physiologic anemia of pregnancy results from disproportionate expansion of plasma volume compared to red cell mass 7, 3:
- Plasma volume: Increases by ~1250 mL (48% increase) 3
- Red cell mass: Increases by only 250 mL without iron (18% increase) or 400-450 mL with iron supplementation 3
- Result: Venous hematocrit drops from approximately 40% to 33% in the last trimester 3
This differential change serves a biological purpose: red cell mass rises proportionately to oxygen-carrying needs, while the greater plasma volume increment accommodates increased blood flow to organs requiring less oxygen (skin and kidneys) 3.
Clinical Implications
Screening Timing
- Screen at first prenatal visit to establish baseline 6, 5
- Repeat screening at 24-28 weeks gestation when dilutional anemia is maximal 6, 5
Prevention Strategy
- Initiate 30 mg/day elemental iron supplementation at first prenatal visit to prevent progression beyond physiologic dilution 6, 4
- This early supplementation allows hemoglobin to rise in the third trimester rather than remain suppressed 1
Important Caveat
The frequently observed fall in plasma volume during the last 6 weeks of pregnancy is likely a measurement artifact due to poor tracer mixing when women lie supine and obstruct circulation to lower limbs, not a true physiologic change 3.