Physiologic Anemia of Pregnancy: Timing and Nadir
Physiologic anemia of pregnancy begins in the first trimester (within the first 8–12 weeks of gestation) and reaches its nadir (lowest point) in the second trimester, typically around 24–28 weeks gestation. 1
Timeline of Hemoglobin Decline
Onset: Hemoglobin concentration begins to decline measurably from the pre-pregnancy baseline during weeks 1–12 of the first trimester, with the physiologic decline starting early in pregnancy. 1
Nadir: The lowest hemoglobin levels occur in the second trimester, specifically around 24–28 weeks of gestation. 1
Recovery: In the third trimester, hemoglobin levels tend to rise gradually toward pre-pregnancy values when oral iron supplementation is used, but remain lower throughout the third trimester without supplementation. 1, 2
Physiologic Mechanism
Plasma volume expands by approximately 40–50% during pregnancy, while red cell mass increases only 20–30%, producing a dilutional (hemodilution) reduction in hemoglobin rather than true anemia. 3, 1, 4
This dilutional effect begins in the first trimester and peaks at 34–36 weeks gestation, though the hemoglobin nadir occurs earlier at 24–28 weeks. 1, 4
There is little plasma volume increase during the first trimester, followed by a progressive rise to maximum at about 34–36 weeks. 4
Trimester-Specific Anemia Thresholds
Understanding when physiologic anemia occurs requires knowing the diagnostic cutoffs:
First trimester: Hemoglobin < 11.0 g/dL defines anemia. 1, 5
Second trimester: Hemoglobin < 10.5 g/dL defines anemia (reflecting the physiologic hemodilution at its peak). 1, 5
Third trimester: Hemoglobin < 11.0 g/dL defines anemia. 1, 5
Clinical Pitfall to Avoid
High hemoglobin levels (>14.6 g/dL or hematocrit >45%) in early pregnancy indicate inadequate plasma volume expansion and are associated with increased risk of stillbirth, maternal hypertension, fetal growth restriction, and preterm delivery. 1, 6
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. 1, 6