Second-trimester pregnancy associated plasma protein-A levels are reduced in Cornelia de Lange syndrome pregnancies

Abstract

Maternal serum samples were collected from 19 pregnancies which resulted in the birth of a child with the classical Cornelia de Lange syndrome phenotype ascertained by careful clinical review. Using specific immunoassays, the serum levels of pregnancy associated plasma protein‐A, free‐beta human chorionic gonadotrophin and inhibin A were investigated. Pregnancy associated plasma protein‐A was detectable in all cases but the levels were significantly reduced in second‐trimester maternal serum from 18 affected pregnancies. Expressed as multiples of the median (MOM), the results ranged from 0.03 MOM to 0.71 MOM with an overall median value of 0.21 MOM (Mann–Whitney p<0.001). From these data it is possible to estimate a probability that any given level of this serum marker is associated with an affected pregnancy. One further sample taken in the first trimester from an affected pregnancy at 11 weeks' gestation had a normal pregnancy associated plasma protein‐A level (1.22 MOM). Less markedly reduced levels were found for free beta human chorionic gonadotrophin and inhibin A. We conclude that second‐trimester maternal serum pregnancy associated plasma protein‐A measurements may be of value as an adjunct to ultrasonography in the prenatal diagnosis of Cornelia de Lange syndrome. A table of likelihood ratios is presented. Copyright © 1999 John Wiley & Sons, Ltd.

Expression of pregnancy-associated plasma protein A2 during pregnancy in human and mouse

“…Moreover, PAPPA is secreted into the maternal circulation (Folkersen et al 1981), and can be a useful marker for certain diseases and pregnancy complications. For example, unusually low levels of PAPPA in the first trimester may be indicative of increased risk of fetal genetic disorders such as Down's syndrome (Brambati et al 1993) and Cornelia de Lange syndrome (Aitken et al 1999). Furthermore, low circulating PAPPA levels are also associated with higher risk of low birth weight, IUGR, and preeclampsia , Kwik & Morris 2003, Dugoff et al 2004, Spencer et al 2008, which are characterized by impaired trophoblast invasion.…”

Low Unconguted Estriol Levels in the Maternal Quadruple-Marker Screen in a Fetus with Cornelia de Lange Syndrome and a Partial Deletion of the <i>NIPBL</i> Gene

“…Similarly, low first and second trimester maternal serum pregnancy-associated plasma protein A (PAPP-A) have been associated with CdLs. The difficulty here is that PAPP-A measurements must be taken over a period of time, and PAPP-A is not a fetal analyte that is routinely measured in maternal serum during second trimester pregnancy screening tests [3,4,5].…”

Prenatal screening characteristics in Emanuel syndrome: a case series and review of the literature

“…Biochemical screening patterns Except for the known biochemical screening patterns of common trisomies and triploidies, conditions that result in specific and abnormal analyte levels include rare conditions caused by abnormal enzyme pathways such as sulphatase Abnormal male genitalia deficiency (with low serum estriol) and the unexplained association between low PAPP-A and Cornelia De Lange syndrome [4]. If any association between Emanuel syndrome and prenatal screening was likely to exist, we suspect that the association would be with an increased nuchal translucency and possibly low PAPP-A, given the incidence of cardiac anomalies and growth restriction.…”