Physiologic Changes in Pregnancy

Biochemical Markers

ALP levels increase beginning in the second trimester and continue rising through the third trimester, with levels reaching up to twice the upper limit of normal, due to placental production 1, 2, 3
The American Association for the Study of Liver Diseases is not cited for this fact, however, the fact that this elevation is of placental origin, not hepatic, and does not indicate liver pathology is supported by 1, 2
If ALP is elevated with normal GGT, bilirubin, and aminotransferases, this represents normal pregnancy physiology 1, 2
Any elevation in aminotransferases, bilirubin, or bile acids is abnormal and requires investigation, even in pregnancy 2
Monitor for concurrent preeclampsia, intrahepatic cholestasis of pregnancy (ICP), or HELLP syndrome if other symptoms develop 2

Albumin levels physiologically decrease during the second half of pregnancy due to hemodilution 1, 2, 3
Blood volume and plasma volume increase substantially during pregnancy, creating a dilutional effect on albumin concentration 1, 3
Total body protein actually increases during pregnancy, with approximately 925 grams of additional protein accumulating 4, 5
40% of the additional protein goes to the fetus, placenta, and amniotic fluid, while 60% goes to maternal tissues 4, 5
Protein synthesis increases by 15% in the second trimester and 25% in the third trimester, while amino acid catabolism decreases 4, 5
Plasma amino acid concentrations decrease as a conservation mechanism 4, 5

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, and both normalize postpartum 1, 2
Do not misinterpret low albumin as malnutrition or liver dysfunction without other supporting evidence 1, 2
Do investigate if aminotransferases (ALT/AST), bilirubin, or bile acids are elevated, as these should remain normal 2

Alkaline phosphatase (ALP) levels physiologically increase during pregnancy, particularly in the second and third trimesters, due to placental production 6, 7, 8
This elevation is considered a normal finding and does not indicate pathology, according to the American Association for the Study of Liver Diseases 8, 9

The American College of Radiology guidelines note that ALP levels are "physiologically higher in childhood, associated with bone growth, and in pregnancy, due to placental production" 6, 7
During pregnancy, the placenta becomes a significant source of alkaline phosphatase production 7, 9

When evaluating liver function tests in pregnant women, it's essential to recognize that elevated alkaline phosphatase alone is expected, as stated by the Gastroenterology guidelines 9
If alkaline phosphatase elevation is accompanied by other abnormal liver tests, further evaluation is warranted, according to the Gastroenterology guidelines 9
To differentiate between hepatic and placental sources of elevated alkaline phosphatase, gamma-glutamyl transferase (GGT) can be measured, as it would be elevated in liver disease but not with isolated placental ALP production, as recommended by the American College of Radiology 7

Decreased albumin levels during the second half of pregnancy due to hemodilution, as noted by the American Association for the Study of Liver Diseases 8
Increased alpha-fetoprotein of fetal liver origin, contributing to normal fetal development, according to the American Association for the Study of Liver Diseases 8
Increased clotting factors II, V, VII, X, XII, and fibrinogen, contributing to hypercoagulability, as stated by the American Association for the Study of Liver Diseases 8

The placenta directly produces and secretes alkaline phosphatase into maternal circulation, causing physiologic elevation of serum ALP levels beginning in the second trimester and continuing through the third trimester, reaching up to twice the upper limit of normal 10, 11
The elevation begins in the second trimester and progressively increases through the third trimester as placental mass and metabolic activity expand 12
The American College of Radiology recommends recognizing that the placenta becomes a significant independent source of alkaline phosphatase production during pregnancy, distinct from the liver, bone, intestine, and kidney sources present in non-pregnant individuals 10

The American College of Radiology suggests that isolated ALP elevation with normal GGT, bilirubin, and aminotransferases (ALT/AST) represents a normal pregnancy pattern, whereas ALP elevation accompanied by elevated GGT confirms hepatic origin rather than placental origin 10, 11
The Gastroenterology society notes that any elevation in aminotransferases, bilirubin, or bile acids is abnormal even in pregnancy and requires investigation for conditions like intrahepatic cholestasis of pregnancy, preeclampsia, or HELLP syndrome 12
The American College of Radiology recommends checking GGT to confirm placental (not hepatic) origin if there is clinical concern—GGT remains normal with placental ALP but elevates with hepatic cholestasis 10, 11

Mild to moderate elevations of alkaline phosphatase (up to 2-fold above the upper limit of normal) with normal aminotransferases, bilirubin, and GGT represent normal pregnancy physiology and require no intervention beyond routine prenatal care 13, 14
Alkaline phosphatase physiologically increases beginning in the second trimester and continues rising through the third trimester, reaching up to twice the upper limit of normal due to placental production 13, 14

Intrahepatic cholestasis of pregnancy (ICP) is characterized by pruritus with bile acids >10 μmol/L, typically presenting in the second or third trimester 13, 14

The American College of Gastroenterology recommends that any elevation in aminotransferases, bilirubin, or bile acids is abnormal even in pregnancy and requires immediate investigation, although the exact recommendation is not provided in the given citations 13, 14

The American Gastroenterological Association suggests that elevated ALP should not be assumed to indicate liver disease in pregnancy when other liver tests are normal 13, 14
The American College of Gastroenterology implies that extensive hepatobiliary workup should not be ordered for isolated ALP elevation, and GGT should be measured first to confirm placental origin 13, 14
Intrahepatic cholestasis of pregnancy (ICP) should not be diagnosed based on elevated ALP alone, as bile acids must be >10 μmol/L with pruritus for diagnosis 13, 14