From the Guidelines
Alkaline phosphatase (ALP) elevation during pregnancy is generally a normal finding and typically does not require intervention, unless accompanied by other abnormal liver function tests or symptoms suggestive of a pathologic condition. During pregnancy, ALP levels can increase to 2-4 times the normal range, particularly in the third trimester, due to the placenta's production of its own ALP isoenzyme and increased bone turnover to support fetal skeletal development 1. These elevations usually resolve within 6-12 weeks postpartum without treatment. However, if ALP levels are extremely high (more than 4 times the upper limit of normal) or accompanied by other abnormal liver function tests, such as elevated bile acids, further evaluation may be warranted to rule out conditions like preeclampsia, cholestasis of pregnancy, or other liver disorders 1. In these cases, additional testing, such as gamma-glutamyl transferase (GGT) or ALP isoenzyme analysis, might help distinguish between physiologic elevation and pathologic causes. Some key conditions to consider in the differential diagnosis include:
- Intrahepatic cholestasis of pregnancy (ICP), characterized by pruritus and elevated bile acids, which can be diagnosed based on a serum bile acid level >10 mmol/L and treated with ursodeoxycholic acid 1
- Hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome, which can present with abdominal pain, vomiting, and proteinuria, and is associated with a high risk of maternal and fetal morbidity and mortality 1
- Acute fatty liver of pregnancy (AFLP), which can present with abdominal pain, vomiting, and polydipsia/polyuria, and is associated with a high risk of maternal and fetal morbidity and mortality 1 Regular prenatal care with appropriate monitoring is sufficient for managing normal pregnancy-related ALP elevations. It is essential to individualize management and consider early delivery in patients with total bile acid levels >100 mmol/L, as the risk of stillbirth increases in this group after 35 weeks 1.
From the Research
Alk Phos Elevation in Pregnancy
- Alkaline phosphatase (ALP) is an enzyme produced by the liver, small intestine, bone, and kidneys as well as the placenta during pregnancy 2.
- ALP levels may increase up to twice the normal limit during pregnancy secondary to placental release and fetal bone growth 2, 3, 4.
- Rare case reports of extremely elevated levels of ALP during pregnancy have demonstrated possible association with adverse pregnancy outcomes, such as preterm delivery, preeclampsia, and intrahepatic cholestasis of pregnancy 2, 5.
Causes and Associations
- The elevation of ALP in pregnancy can be of placental origin, with some studies suggesting that it may be a marker for placental insufficiency or underlying placental damage 3, 5.
- Other studies have reported associations between extremely elevated ALP levels and adverse perinatal outcomes, including gestational diabetes mellitus and hypertensive disorders 5.
- However, some cases have reported no perinatal complications or normal labor at term, despite extremely elevated ALP levels 3, 4.
Clinical Implications
- The presence of extremely elevated ALP levels in pregnancy should prompt further evaluation and monitoring, as it may be associated with underlying placental damage or other adverse pregnancy outcomes 2, 5.
- However, an isolated, marked rise in ALP should not be relied upon exclusively to dictate the approach in the absence of other fetomaternal considerations 3.