Can pregnancy cause elevated alkaline phosphatase (ALP) and low protein levels?

Elevated ALP and Low Protein in Pregnancy

Yes, pregnancy physiologically causes both elevated alkaline phosphatase (ALP) and decreased albumin/protein levels as normal adaptations, particularly in the second and third trimesters. 1, 2

Elevated Alkaline Phosphatase in Pregnancy

ALP elevation is an expected normal finding during pregnancy due to placental production. 2

• ALP levels increase beginning in the second trimester and continue rising through the third trimester 1
• The placenta becomes a significant source of ALP production, contributing to levels that can reach up to twice the upper limit of normal 2, 3
• This elevation is of placental origin, not hepatic, and does not indicate liver pathology 1, 2
• The American Association for the Study of Liver Diseases explicitly states this is a normal physiologic change that requires no intervention 2

Differentiating Normal from Pathologic ALP Elevation

To distinguish placental from hepatic ALP elevation, measure gamma-glutamyl transferase (GGT): 2

• GGT remains normal with isolated placental ALP production 2
• GGT elevates if the ALP source is hepatic/cholestatic liver disease 2
• If ALP is elevated with normal GGT, bilirubin, and aminotransferases, this represents normal pregnancy physiology 1

When to Investigate Further

Any elevation in aminotransferases, bilirubin, or bile acids is abnormal and requires investigation, even in pregnancy. 1

• Isolated ALP elevation alone (even extreme elevations up to 30-fold) can occur in uncomplicated pregnancies 3, 4, 5
• However, some case reports suggest extreme ALP elevations (>10-fold) may associate with placental insufficiency, IUGR, or preterm delivery 6, 7
• Monitor for concurrent preeclampsia, intrahepatic cholestasis of pregnancy (ICP), or HELLP syndrome if other symptoms develop 1, 6

Low Protein/Albumin in Pregnancy

Albumin levels physiologically decrease during the second half of pregnancy due to hemodilution. 1, 2

Mechanism of Protein Changes

• Blood volume and plasma volume increase substantially during pregnancy, creating a dilutional effect on albumin concentration 1
• Despite lower circulating concentrations, total body protein actually increases during pregnancy 1
• Approximately 925 grams of additional protein accumulates during pregnancy (148g nitrogen equivalent) 1
• 40% goes to fetus, placenta, and amniotic fluid; 60% to maternal tissues (uterus, breasts, blood volume, extracellular fluid) 1

Metabolic Adaptations

Pregnancy induces protein-conserving metabolic changes: 1

• Protein synthesis increases by 15% in second trimester and 25% in third trimester 1
• Amino acid catabolism decreases, with reduced urea synthesis and urinary urea excretion 1
• Plasma amino acid concentrations decrease (especially glucogenic amino acids and urea cycle amino acids) as a conservation mechanism 1

Clinical Implications

The combination of elevated ALP and low albumin in pregnancy is physiologically normal and expected. 1, 2

• These changes begin in the first trimester for albumin and second trimester for ALP 1
• Both normalize postpartum, with ALP returning to baseline within weeks to months after delivery 3, 6, 4, 5
• No intervention is needed for these isolated findings in an otherwise healthy pregnancy 2

Key Pitfalls to Avoid

• Do not assume liver disease based solely on elevated ALP in pregnancy 2
• Do not misinterpret low albumin as malnutrition or liver dysfunction without other supporting evidence 1
• Do investigate if aminotransferases (ALT/AST), bilirubin, or bile acids are elevated, as these should remain normal 1
• Consider pathology if ALP elevation is accompanied by elevated GGT, suggesting hepatic rather than placental origin 2