Elevated Alkaline Phosphatase in Pregnancy with Normal Bilirubin
An ALP of 700 U/L with normal bilirubin in pregnancy is physiologically normal and requires no intervention beyond routine prenatal care, as placental production causes ALP to rise up to 2-fold above the upper limit of normal starting in the second trimester. 1, 2
Understanding the Physiologic Basis
Pregnancy causes predictable ALP elevation through placental production, not liver disease. The placenta directly produces and secretes alkaline phosphatase into maternal circulation beginning in the second trimester, with progressive increases through the third trimester reaching up to twice the upper limit of normal. 2 This elevation is entirely distinct from hepatic, bone, intestinal, or kidney sources of ALP present in non-pregnant individuals. 2
- Both bone and placental isoenzymes contribute to total ALP elevation during pregnancy, with bone ALP significantly elevated by 31-32 weeks gestation and placental ALP predominating by 38 weeks. 3
- The combination of elevated ALP with normal bilirubin and normal aminotransferases represents expected pregnancy physiology, not pathology. 2, 4
Critical Diagnostic Algorithm
Measure GGT immediately to confirm placental (not hepatic) origin of the ALP elevation. 1, 2
If GGT is Normal:
- This confirms placental origin and represents normal pregnancy. 2
- No further hepatobiliary workup is indicated. 2
- Continue routine prenatal care only. 2
If GGT is Elevated:
- This indicates hepatic cholestasis requiring immediate investigation. 1, 2
- Measure bile acids to evaluate for intrahepatic cholestasis of pregnancy (ICP), which requires bile acids >10 μmol/L with pruritus for diagnosis. 2
- Obtain abdominal ultrasound to assess for choledocholithiasis (the most common cause of jaundice in pregnant women in the current era, accounting for 25% of cases). 5
- If ultrasound is negative but GGT remains elevated, proceed to MRI with MRCP. 1
Red Flags Requiring Urgent Investigation
Any elevation in aminotransferases (ALT/AST), bilirubin, or bile acids is abnormal even in pregnancy and requires immediate investigation. 2
- Elevated aminotransferases with ALP elevation: Consider preeclampsia/HELLP syndrome (24% of jaundice cases in pregnancy), acute fatty liver of pregnancy, or viral hepatitis. 5, 6
- Elevated bilirubin with ALP elevation: Most commonly indicates gallstones (25%), preeclampsia-related disorders (24%), or intrahepatic cholestasis of pregnancy (13%). 5
- Pruritus with elevated bile acids: Diagnostic of intrahepatic cholestasis of pregnancy, which carries increased fetal risk and requires ursodeoxycholic acid treatment. 4
Common Clinical Pitfalls to Avoid
Do not order extensive hepatobiliary workup for isolated ALP elevation with normal GGT, bilirubin, and aminotransferases. 2 This represents normal pregnancy physiology and does not indicate liver disease. 1, 2
Do not diagnose intrahepatic cholestasis of pregnancy based on elevated ALP alone. 2 ICP requires both bile acids >10 μmol/L and pruritus for diagnosis. 2
Do not assume elevated ALP indicates liver disease when other liver tests are normal. 2 In pregnancy, isolated ALP elevation up to 2-fold above the upper limit of normal is expected and benign. 2
Severity Classification Context
- Mild ALP elevation: <5× upper limit of normal 1
- Moderate ALP elevation: 5-10× upper limit of normal 1
- Severe ALP elevation: >10× upper limit of normal 1
An ALP of 700 U/L (assuming normal range ~30-120 U/L) represents approximately 6× the upper limit of normal, which would be classified as moderate elevation. 1 However, in the context of pregnancy with normal bilirubin and presumably normal aminotransferases, this still represents physiologic placental production rather than pathology, provided GGT is normal. 2