Placental mosaicism is associated with unexplained second-trimester elevation of MShCG levels, but not with elevation of MSAFP levels.

In this patient-control study, we examined the impact of placental mosaicism on the concentrations of maternal serum human chorionic gonadotropin (MShCG) and maternal serum alpha-fetoprotein (MSAFP) in the second trimester of pregnancy. Patient and control groups were selected from 2347 women with a singleton pregnancy, who underwent chorionic villous sampling in the first trimester and from whom second-trimester serum samples had been collected. The concentrations of both serum markers, expressed in multiples of the median (MOM), in 35 women with confined placental mosaicism (CPM) were compared with those in 70 controls with uncomplicated pregnancies. Elevated MSAFP or MShCG was defined as a concentration of > or = 2.0 MOM. Of the 35 pregnancies with CPM, none had an elevated MSAFP level, as opposed to two out of the 70 women (2.9 per cent) in the control group (P = NS). Nine women in the placental mosaicism group (26 per cent) had an MShCG level of > or = 2.0 MOM, compared with five in the control group (7.1 per cent; P = 0.0135). Nineteen women in the placental mosaicism group (54 per cent) were screen-positive for Down's syndrome (cut-off 1:250), compared with 17 women (24 per cent) in the control group (P = 0.0042; relative risk = 2.3). The three highest MShCG levels were found in pregnancies with CPM that involved trisomy 16; all these women delivered a small-for-gestational age (SGA) infant. CPM, especially with trisomy 16, is associated with elevated levels of MShCG, but not with elevated levels of MSAFP. It is an important cause of false-positive results in serum screening programmes for fetal Down's syndrome. It is possible that abnormal MShCG levels in pregnancies with CPM result from dysfunctional placenta, caused by chromosomally abnormal areas. We therefore recommend increased surveillance of pregnancies with unexplained elevated MShCG levels.