Alkaline phosphatase (ALP) is a common enzyme found throughout the body, primarily in the liver, bones, kidneys, and intestines. During pregnancy, the placenta introduces a substantial additional source of ALP, causing its levels in the maternal bloodstream to change significantly. Understanding these shifts requires distinguishing between the normal physiological rise and elevations that may signal a health complication.
The Specific Source and Function of Alkaline Phosphatase During Gestation
The increase in total ALP levels during pregnancy is primarily due to Placental Alkaline Phosphatase (PLAP). This specific isoform is synthesized by the syncytiotrophoblasts, the cells forming the outer layer of the placenta. PLAP is released into the maternal circulation early in gestation and increases progressively as the placenta grows.
The exact biological role of PLAP is still being studied, but its location suggests a function at the maternal-fetal interface. It is theorized that the enzyme facilitates nutrient and energy exchange, potentially playing a role in calcium regulation or metabolite transport. Since this placental isoform is distinct from other ALP sources, specialized isoenzyme tests can confirm the placenta as the origin of an elevated total ALP level.
Normal Range and Expected Changes Across Trimesters
Total ALP measurement combines background enzymes from the liver and bone with the placental isoform. Consequently, the normal reference range for ALP changes significantly as gestation advances. During the first trimester, ALP levels are often similar to or slightly lower than those in a non-pregnant individual, typically falling between 17 to 88 Units per Liter (U/L).
The rise in ALP usually begins near the end of the first trimester and continues throughout the second, driven by the placenta’s increasing size and metabolic activity. By the third trimester, ALP concentration can be two to four times higher than the non-pregnant upper limit. A common third-trimester range may extend up to 229 U/L or higher. Clinicians must use these pregnancy-specific reference ranges to avoid misinterpreting this normal physiological change as disease.
Clinical Significance of Elevated Alkaline Phosphatase Levels
When total ALP levels exceed the expected range for a specific gestational age, it may signal a pathological process involving the liver or the placenta. Intrahepatic Cholestasis of Pregnancy (ICP), a liver condition causing bile acid buildup, is a common hepatic cause. However, due to the substantial physiological rise in PLAP, ALP is not a reliable standalone diagnostic marker for ICP; diagnosis focuses on elevated serum bile acids and other liver enzymes.
Elevated ALP may indicate placental damage or dysfunction. The placental isoform has been observed to increase significantly in cases of severe preeclampsia or HELLP syndrome, which involve damage to the placental lining. Extremely high ALP levels may be associated with adverse outcomes, including placental insufficiency, preterm delivery, and fetal growth restriction. Isoenzyme testing can help differentiate the placental source from liver or bone sources to pinpoint the origin of the elevation.
Clinical Significance of Low Alkaline Phosphatase Levels
While high ALP levels are more commonly discussed, an abnormally low level is also clinically significant. Low ALP is a less frequent finding, but it may reflect inadequate nutritional status, including deficiencies in zinc, magnesium, or protein. Low levels can also be associated with hypothyroidism, an underactive thyroid gland.
In the context of placental health, low ALP levels correlate with a reduced placental size or diminished enzyme production capacity. This reduced output has been linked to an increased risk for adverse outcomes, specifically intrauterine growth restriction (IUGR). Although extremely rare causes include hypophosphatasia, low ALP in pregnancy is primarily addressed by evaluating maternal nutritional status and monitoring fetal growth.