What causes high AFP?

Alexander Kofinas M.D.

Because AFP normally finds its way into the maternal circulation via the amniotic fluid, anything that increases the amount of AFP in the former will consequently amplify the concentration of AFP in the latter. Such conditions include, open neural tube defects (spina bifida and anencephaly), abdominal wall defects (omphalocele and gastroschisis), sacrococcygeal teratomas (tumors of the lower spine), and other anatomical defects. Excessive fetal urine levels of AFP can occur in cases of fetal renal damage where the kidneys excrete abundant amounts of alpha-fetoprotein. One such condition is called Finnish Nephrosis and is extremely rare (1 in 3000 individuals of Finnish descent). Some conditions may also increase maternal serum AFP in ways other than through the amniotic fluid. In such cases, the AFP finds its way into the maternal circulation directly through the damaged placental vessels. This damage may be the result of endothelial inflammation and breakdown, which leads to leakage of fetal AFP into the maternal vascular space. This may be the most dangerous of all conditions, because it is commonly linked to placental failure with all the usual consequences ranging from fetal growth failure to fetal death. A study in Great Britain recently found that there is a direct relationship between sudden infant death syndrome (SIDS) and elevated AFP. In most instances of elevated AFP due to placental damage, the initial cause is placental thrombosis brought on by acquired or genetic thrombophilia.