Total Serum Calcium is Decreased in Normal Pregnancy
Total serum calcium progressively declines throughout normal pregnancy, falling from approximately 4.80 mEq/L in the first trimester to 4.46 mEq/L in the third trimester, primarily due to physiologic hypoalbuminemia rather than true hypocalcemia. 1, 2
Physiologic Changes in Calcium Homeostasis
Total vs. Ionized Calcium
- Total serum calcium decreases continuously during pregnancy, beginning in the first trimester and continuing until approximately 32 weeks' gestation, with mean values declining from 4.80 mEq/L to 4.46 mEq/L across trimesters 2
- This decline parallels the progressive fall in albumin concentration that occurs with pregnancy-related hemodilution 3, 1
- Ionized (free) calcium remains essentially stable throughout pregnancy, declining only minimally from 2.33 mEq/L to 2.24 mEq/L, representing a physiologically insignificant change 2, 4
- The proportion of total calcium represented by the ionized component actually increases progressively during gestation because the bound fraction falls more dramatically 2
Parathyroid Hormone Response
- PTH levels initially decline in early pregnancy but then progressively increase, rising 33-53% above early pregnancy values by term 1
- This "physiologic hyperparathyroidism" represents a compensatory response to maintain calcium homeostasis in the face of expanded fluid volume, increased renal calcium excretion, and placental calcium transfer 1, 5
- The PTH increase appears to be secondary to the slight decrease in ionized calcium that occurs after 21-25 weeks' gestation (from 3.81 mg/dL to 3.63 mg/dL) 4
- PTH levels remain within or just above the reference interval for non-pregnant women throughout most of pregnancy 6
Calcitonin Patterns
- Calcitonin levels show highly variable and inconsistent patterns during pregnancy, with no uniform directional change 1
- Approximately half of pregnant women demonstrate increased calcitonin during the first and second trimesters followed by a decline in the third trimester, while the other half show either no change or progressively falling levels 1
- Mean calcitonin levels remain just above the reference interval for non-pregnant women throughout pregnancy 6
Clinical Monitoring Implications
Laboratory Interpretation
- Albumin levels decrease during the second half of pregnancy due to hemodilution, making correction of total calcium for albumin essential for accurate interpretation 3
- Ionized calcium should be measured directly when subtle changes are clinically important, though this is more expensive and less reproducible than total calcium measurement 3
- During pregnancy, serum calcium should be assessed together with phosphate, magnesium, and PTH at least once per trimester 3, 7
Other Biochemical Changes
- Alkaline phosphatase progressively increases throughout pregnancy, reaching markedly high levels at term due to placental production 3, 8, 6
- Phosphate levels remain unchanged and within the reference interval for non-pregnant women 6
- Urinary calcium excretion remains constantly elevated, close to the upper reference limit, despite enhanced renal calcium conservation 6
Common Pitfalls
- Do not interpret decreased total calcium as pathologic hypocalcemia without correcting for albumin or measuring ionized calcium, as the decline is physiologic 1, 2
- Non-pregnant reference limits for total calcium are not valid during pregnancy and should not be used for clinical decision-making 6
- Decreased serum calcium during pregnancy may occur due to decreased 1,25-dihydroxyvitamin D3 and decreased calcitonin levels, predisposing some women to insufficiency fractures, though this is rare 3