Reduced fetal hepatic alpha‐fetoprotein levels in Down' S syndrome

AbstractIn the majority of pregnancies involving a Down' s syndrome (DS) fetus, the level of alpha‐fetoprotein (AFP) measured in maternal serum and amniotic fluid is reduced to about 70 per cent of the level attained in normal pregnancies. Causes of this decrease may include the production of an altered AFP molecule with modified turnover or transport properties, or a reduction in the level of AFP synthesis. We examined hepatic AFP mRNA transcripts and compared AFP polypeptide isoforms in liver tissue samples obtained from a group of DS and normal abortuses. No difference was detected in the structure of the AFP mRNA transcript or in the charge or mass of AFP polypeptides in the two sample groups. However, the hepatic AFP level, expressed as μg AFP/mg protein, was significantly lower in a group of 28 DS cases relative to a group of 47 normal controls (P = 0·04). This difference in hepatic AFP concentration did not appear to be the result of a general reduction in the level of total protein or total RNA production. The greatest difference between the AFP levels of the DS and normal groups was observed in the earliest samples examined (i.e., at 17–19 weeks of age) where the median AFP levels differed by about 20 per cent.