Anion Gap (serum/plasma)
The anion gap increases slightly in normal pregnancy (≈1–2 mmol/L) due to physiologic changes in albumin and unmeasured anions. Interpretation must incorporate acid–base status, albumin concentration, and clinical context.
| Units | Nonpregnant Adult | 1st Trimester | 2nd Trimester | 3rd Trimester |
|---|---|---|---|---|
| mmol/L | 10 – 17 | 10 – 20 | 10 – 18 | 11 – 18 |
Formula: (Na⁺ + K⁺) − (Cl⁻ + HCO₃⁻)
See also: Anion Gap Calculator
Causes of high anion gap
- Pregnancy-related
- Diabetic ketoacidosis
- Starvation or hyperemesis ketoacidosis
- Lactic acidosis (sepsis, hemorrhage, severe preeclampsia)
- Acute renal failure (uremic acidosis)
- Toxin ingestion (salicylates, methanol, ethylene glycol, acetaminophen pyroglutamic acidosis)
- General causes
- Ketoacidosis (diabetic, alcoholic, starvation)
- Shock or hypoxia
- Renal failure
- Toxins (methanol, ethylene glycol, salicylates, cyanide)
- Severe rhabdomyolysis or ischemic bowel
High anion gap metabolic acidosis is never normal in pregnancy and requires urgent evaluation for ketoacidosis, shock, or sepsis.
Causes of normal or low anion gap
- Normal AG (hyperchloremic) acidosis
- GI bicarbonate loss (diarrhea, fistula)
- Renal tubular acidosis
- Large-volume normal saline infusion
- Low anion gap
- Hypoalbuminemia (most common; common in pregnancy)
- Paraproteinemia (multiple myeloma)
- Lab artifact (hyperlipidemia, hyperproteinemia)
- Unmeasured cations (lithium, hypermagnesemia, severe hypercalcemia)
Correcting the anion gap for albumin may improve interpretation in pregnancy, where albumin is physiologically reduced.
References
- Lockitch G. Handbook of Diagnostic Biochemistry and Hematology in Normal Pregnancy. CRC Press; 1993.
- Kratz A et al. Laboratory reference values. N Engl J Med. 2004;351:1548–63.
- Abbassi-Ghanavati M, Greer LG, Cunningham FG. Pregnancy and laboratory studies. Obstet Gynecol. 2009;114:1326–31.
- Kraut JA, Madias NE. Serum anion gap: uses and limitations. Clin J Am Soc Nephrol. 2007;2:162–74.