Maternal serum human chorionic gonadotrophin and pregnancy‐associated plasma protein a, markers for fetal down syndrome at 8–14 weeks

Abstract

Maternal serum levels of human chorionic gonadotrophin and its subunits (intact, alpha, and free beta h CG) and pregnancy-associated plasma protein A (PAPP-A) were measured in 279 women between 8 and 14 weeks' gestation. This group included 23 pregnancies in which the fetus had Down syndrome (DS), diagnosed either at birth or during the second trimester (n = 17) or from chorionic villus sampling (CVS) (n = 6). Normal medians were determined from the 258 apparently normal pregnancies. The median levels of intact hCG (1.4 MOM) and free beta hCG (2.1 MOM) were significantly raised, whereas the median level of PAPP-A (0.39 MOM) was significantly lower in the DS pregnancies when compared with the control group. Levels of alpha hCG were similar in both the control and the DS pregnancies. Analysis of samples taken prior to 14 weeks' gestation demonstrated that only PAPP-A (0.34 MOM) was significantly altered in DS pregnancies. However, after the exclusion of DS cases diagnosed at CVS, the median intact hCG (1.56 MOM), free beta hCG (2.27 MOM), and alpha hCG (1.8 MOM) were all raised in DS pregnancies. This emphasizes the problem of the interpretation of biochemical markers when DS cases are diagnosed at CVS.

The proform of eosinophil major basic protein: a new maternal serum marker for Down syndrome

“…The relationship between these clinical parameters does not, however, seem to be straightforward (Wagner et al, 1993). The maternal serum concentration of PAPP-A in DS pregnancies has consistently been found to be reduced to 20-40 per cent of the level in maternal sera from normal pregnancies in the first trimester (Wald et al, 1992;Muller et al, 1993;Macintosh et al, 1994;Brambati et al, 1994;Spencer et al, 1994;Casals et al, 1996;Krantz et al, 1996;Qin et al, 1996Qin et al, , 1997aForest et al, 1997), and PAPP-A seems to be the most promising serum marker for DS screening in the first trimester (Wald et al, 1996). It is very likely, that proMBP is perturbed in some periods in gestation in DS pregnancies, and a diagnostic use of this could lead to an improvement of established maternal serum screening practices.…”

First-Trimester Combined Screening Is Effective for the Detection of Unbalanced Chromosomal Translocations at 11 to 12 Weeks of Gestation

“…8,9 Fetal chromosomal aberrations, including common trisomies (21, 18, and 13) and sex chromosome aneuploidy, have been associated with low levels of maternal serum PAPP-A. [10][11][12][13][14][15] Likewise, low maternal serum PAPP-A levels at the first trimester have been associated with an increased frequency of adverse obstetrical outcomes. 16,17 Therefore, a low level of PAPP-A in circulation may result in abnormal placental function and represents a sensitive indicator of different types of aneuploidies ranging from triploidies to unbalanced chromosomal translocations.…”

FIRST-TRIMESTER BIOCHEMICAL SCREENING FOR DOWN SYNDROME WITH THE USE OF PAPP-A, AFP, AND β-hCG

“…PAPP-A is detectable in maternal serum by about the 30th day of pregnancy and MS-PAPP-A levels increase exponentially until term, then gradually decrease and are undetectable by the sixth postpartum week (Sinosich, 1985). MS-PAPP-A concentrations are significantly reduced in the presence of a fetus with DS, suggesting this as a sensitive marker during the first trimester (Brambati et al, 1991(Brambati et al, , 1994Cuckle and Lilford, 1992;Wald et al, 1992;Hurley et al, 1993;Bersinger et al, 1994;Macintosh et al, 1994;El Farra and Grudzinskas, 1995).…”