Transferrin (serum) — Reference Values During Pregnancy

Transferrin is synthesized by the liver and its concentration is regulated primarily by iron status and hormonal influences:

• Estrogen-driven synthesis: Rising estrogen levels in pregnancy stimulate hepatic production of transferrin. As a result, both transferrin and total iron-binding capacity (TIBC) increase progressively across gestation.
• Support for expanded erythropoiesis: Maternal plasma volume expansion, increased red cell mass, and fetal–placental iron requirements increase iron turnover. Higher transferrin concentrations enhance iron transport to the bone marrow and placenta.
• Relationship to iron stores: Transferrin usually rises as iron stores (ferritin) fall, reflecting a compensatory response to mobilize and transport iron. Thus, elevated transferrin with low ferritin is typical of iron deficiency.
• Transferrin saturation: Because serum iron often falls while transferrin rises, transferrin saturation (serum iron ÷ TIBC) may decrease in late pregnancy, even when hemoglobin remains in the normal range.
• Clinical implication: Interpretation of iron status in pregnancy should consider hemoglobin/hematocrit, ferritin, transferrin/TIBC, and transferrin saturation rather than any single value alone.

Low transferrin generally reflects reduced hepatic synthesis, severe protein depletion, or profound systemic illness. Examples include:

• Chronic liver disease (cirrhosis, advanced hepatitis)
• Severe protein–calorie malnutrition or cachexia
• Nephrotic syndrome with urinary loss of proteins
• Chronic inflammation or infection (negative acute-phase reactant)
• Hemochromatosis or iron overload (downregulation of transferrin)
• Severe systemic illness, sepsis, or major trauma
• Rare genetic defects in transferrin synthesis (extremely uncommon; usually associated with marked iron overload and anemia)

In pregnancy, low transferrin is uncommon and should prompt evaluation for significant liver disease, malnutrition, or chronic inflammatory conditions.

High transferrin is most often associated with increased estrogen exposure or iron deficiency:

• Pregnancy — physiologic increase due to estrogen and increased iron demand.
• Iron deficiency — classic cause of elevated transferrin and TIBC with low ferritin and low transferrin saturation.
• Oral contraceptive or estrogen therapy — estrogen-induced hepatic synthesis.
• Chronic blood loss (e.g., heavy menstrual bleeding, GI bleeding) with iron deficiency.
• Late pregnancy with inadequate iron supplementation — high transferrin/TIBC, low ferritin, borderline or low hemoglobin.
• Recovery from acute illness — as negative acute-phase effects resolve, transferrin can rebound above baseline in the setting of iron deficit.

When serum transferrin or TIBC is elevated in pregnancy, assessment of ferritin, hemoglobin, mean corpuscular volume, and transferrin saturation helps confirm iron deficiency and guide replacement therapy.

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