Alkaline Phosphatase (ALP)

During pregnancy, ALP levels naturally rise, particularly in the third trimester, due to increased production from the placenta. Both high and low levels may be used to assess placental health and function. In this article, we’ll cover optimal ALP ranges and potential causes of abnormalities.

ALP Testing

Alkaline phosphatase (ALP) measures the total ALP from all isotopes in the blood sample. It is an analyte found on the comprehensive metabolic panel (CMP).

Alkaline phosphatase is a zinc metalloprotein enzyme found in various tissues throughout the body, including the liver, bones, kidney, intestine, and placenta. It is called “alkaline” because it works optimally at a slightly basic or alkaline pH. 

ALP isozymes are variants of the ALP enzyme found in different tissues throughout the body. Each isozyme has slightly different properties and is associated with specific functions. Here are the four main ALP isozymes.

• Bone ALP: This isozyme is primarily found in bone tissue and is produced by osteoblasts, the bone-forming cells. 
• Intestinal ALP: This isozyme is primarily found in the small intestine, particularly in the brush border of the intestinal mucosa. 
• Liver ALP: Liver ALP is produced by hepatocytes in the liver. It is released into the bloodstream when liver cells are damaged, making it a common marker for liver health. 
• Placental ALP: Placental ALP is produced by the placenta during pregnancy. It helps form the maternal-fetal barrier, which separates maternal blood from fetal blood within the placenta. 

ALP in Pregnancy

​During pregnancy, alkaline phosphatase may reach three times the upper normal limit. This increase begins at the end of the first trimester and continues through the third trimester. 

Typically, ALP levels gradually return to nonpregnant or baseline within the first few weeks after childbirth.

High ALP in Pregnancy

There is limited data on the consequences of high ALP in pregnancy, as an increase in ALP is seen in normal pregnancy. It is not an accurate marker of liver function or disease in pregnancy. 

If ALP is increased outside of normal ranges for gestational age, the increase may come from any of the isoform sources. 

Most Common Causes of High ALP in Pregnancy

• Hyperthyroidism
• Intrahepatic Cholestasis of Pregnancy (ICP)
• Bone Loss
• IBD Conditions (Celiac Disease, Crohn's Disease, Ulcerative Colitis)
• Hyperparathyroidism
• Nutritional Deficiencies (vitamin D, calcium)
• Recent Bone Injury
• Liver Disease/Inflammation

Low ALP in Pregnancy

Low ALP in pregnancy has been shown to predict IUGR of the fetus and a high-risk pregnancy.

The low ALP during pregnancy probably reflects a reduced placental size or a decreased ability to produce ALP.

According to a 2023 study published in The Lancet, serum ALP levels (≤116 IU/L) in late pregnancy increase the risk of venous thromboembolism.

Most Common Causes of Low ALP in Pregnancy

• Hypothyroidism
• Low Progesterone
• Nutritional Deficiencies (magnesium, zinc)
• Low Protein Diet
• Malnutrition

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Medical Disclaimer:
This content is for educational purposes only and is intended for licensed medical professionals. It is based on current research, subject to change, and not intended to diagnose, treat, or prevent any medical condition. This information does not replace consultation with a qualified healthcare provider. Seek professional medical evaluation and treatment from a licensed provider. Use of this information is at your own risk.

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