Is elevated alkaline phosphatase (Alk Phos) concerning in pregnancy?

From the Guidelines

Elevated alkaline phosphatase (Alk Phos) during pregnancy is generally not concerning, as it represents a normal physiological change. According to the most recent guidance from the American Association for the Study of Liver Diseases 1, alkaline phosphatase levels typically increase during the second and third trimester due to production from the placenta and fetal bones. This elevation is a normal change that occurs during pregnancy, as outlined in the liver biochemistry changes during normal pregnancy 1.

The physiological increase in alkaline phosphatase occurs because the placenta produces its own isoenzyme of alkaline phosphatase (placental alkaline phosphatase) to support fetal bone development and placental function. However, if Alk Phos levels are extremely high (more than 4 times the upper limit of normal) or if accompanied by other abnormal liver tests like elevated bilirubin or transaminases, further evaluation may be warranted to rule out conditions such as preeclampsia, intrahepatic cholestasis of pregnancy, or other liver disorders 1.

Some key points to consider include:

• Alkaline phosphatase levels increase by 2-4 times normal values during the third trimester
• This elevation begins around week 20 and peaks near delivery
• No treatment or intervention is needed for this normal elevation
• Further evaluation is needed if Alk Phos levels are extremely high or accompanied by other abnormal liver tests
• The diagnosis of intrahepatic cholestasis of pregnancy is based on a serum bile acid level >10 mmol/L in the setting of pruritus, typically during the second or third trimester 1.

After delivery, these elevated levels should return to normal within about 2-3 weeks. It is essential to individualize management and consider early delivery in patients with bile acids >100 mmol/L, as the risk of stillbirth increases in this group after 35 weeks 1.

From the Research

Alkaline Phosphatase Levels in Pregnancy

Elevated alkaline phosphatase (Alk Phos) levels in pregnancy can be a concern, but it's essential to understand the physiological changes that occur during pregnancy.

• Alk Phos levels may increase up to twice the normal limit during pregnancy due to placental release and fetal bone growth 2, 3, 4.
• However, extremely elevated levels of Alk Phos have been associated with adverse pregnancy outcomes, such as preterm delivery, preeclampsia, and intrahepatic cholestasis of pregnancy 3, 5.

Physiological vs. Pathological Elevations

It's crucial to differentiate between physiological and pathological elevations of Alk Phos in pregnancy.

• Physiological elevations are typically seen in the third trimester and return to normal postpartum 2, 6.
• Pathological elevations, on the other hand, may indicate underlying liver, kidney, bone, or malignant diseases 5, 4.

Clinical Implications

Elevated Alk Phos levels in pregnancy should be monitored and investigated further to rule out any underlying conditions.

• In some cases, extremely elevated Alk Phos levels may be an incidental finding, and the patient may have a normal pregnancy outcome 5, 6.
• However, in other cases, elevated Alk Phos levels may be associated with adverse pregnancy outcomes, and close monitoring and management may be necessary 3.