Complement C4 (serum)
Complement C4 increases modestly during pregnancy because of estrogen-stimulated hepatic synthesis and physiologic complement activation.
| Units | Nonpregnant Adult | 1st Trimester | 2nd Trimester | 3rd Trimester |
|---|---|---|---|---|
| mg/dL | 16 – 47 | 9 – 45 | 10 – 42 | 17 – 37 |
| g/L | 0.16 – 0.47 | 0.09 – 0.45 | 0.10 – 0.42 | 0.17 – 0.37 |
Pregnancy physiology
- Mild physiologic increase due to estrogen-mediated hepatic stimulation.
- Part of global complement activation that supports placental and immune function.
- Values peak mid-pregnancy and decline slightly in late gestation.
Causes of decreased C4
- Systemic lupus erythematosus (SLE)
- Lupus nephritis (especially proliferative disease)
- Hereditary angioedema (C1 inhibitor deficiency — hallmark: low C4, normal C3)
- Hereditary complement deficiencies
- Immune complex glomerulonephritis
- Severe liver disease
- Sepsis or massive complement activation
Falling C4 in pregnancy may indicate lupus flare, complement consumption, or hereditary angioedema.
Causes of increased C4
- Normal physiologic rise in pregnancy
- Acute or chronic inflammation
- Obesity and metabolic syndrome
- Hyperestrogenic states (pregnancy, OCPs)
- Corticosteroid therapy
- Lymphoproliferative disorders (less common)
Elevated C4 usually reflects inflammation or estrogen exposure rather than complement activation.
References
- Lockitch G. Handbook of Diagnostic Biochemistry and Hematology in Normal Pregnancy. CRC Press; 1993.
- Abbassi-Ghanavati M, Greer LG, Cunningham FG. Pregnancy and laboratory studies: a reference table for clinicians. Obstet Gynecol. 2009;114:1326–31.
- Wallach J. Interpretation of Diagnostic Tests. 8th ed. Lippincott Williams & Wilkins; 2007.
- Gronowski AM (ed). Handbook of Clinical Laboratory Testing During Pregnancy. Humana Press; 2004.