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Biochemical markers of trisomy 21 and the pathophysiology of Down's syndrome pregnancies

Using biochemical and immunocytochemical methods, we have investigated endogenous levels of various markers in tissues obtained from 67 Down's syndrome pregnancies after therapeutic abortion in the second trimester and in corresponding tissues from unaffected abortuses. Alpha‐fetoprotein (AFP), intact and free beta human chorionic gonadotrophin (hCG), pregnancy‐specific beta‐1 glycoprotein (SP‐1), placental alkaline phosphatase (PALP), pregnancy‐associated plasma protein A (PAPP‐A), and gamma glutamyl transferase (GGT) were investigated in placental tissue; AFP and GGT in fetal liver; and GGT in fetal intestine. The results indicate that maternal serum levels of placental products reflect those found in the placenta: intact hCG, free beta hCG, and SP‐1 levels were elevated in Down's syndrome pregnancies, while PAPP‐A and PALP levels were little changed. This suggests that membrane passage of these markers is not affected but there is altered synthesis of hCG and SP‐1. AFP levels were strikingly elevated in placental homogenates and unchanged in liver homogenates from Down's syndrome pregnancies, while the levels in maternal serum were reduced, pointing to a possible transport defect specific to AFP. GGT levels were high in placenta and liver from Down's syndrome pregnancies but low in fetal intestine. © 1997 John Wiley & Sons, Ltd.