Screening in early pregnancy : more than Down syndrome alone

Abstract

Abstract Since 2004 it was allowed to inform all pregnant women on the possibility of having a screening test for DS, with the first-trimester combined test (maternal serum concentrations of pregnancy-associated plasma protein A (PAPP-A) and the free beta subunit of human chorion gonadotrophin (f?-hCG) between 8-14 weeks of the pregnancy, first-trimester ultrasound measurement of the fetal nuchal translucency and maternal age) as test of choice. Since January 2007, a nationwide screening program is running. Currently, 24% of all pregnant women are involved in the screening for Down syndrome. The detection rate for the first-trimester combined test during the period 2004 - 2006 was 75.9% at a cut-off level of 1 in 250 at term, with a screen-positive rate of 3.3%. The performance of the first-trimester test has improved over the years, but there is still room for further improvements. There is growing evidence that the first-trimester test can also be put to use for a broader screening for foetal and maternal health, including trisomy 13 and 18, preeclampsia (PE), preterm birth, growth restriction, fetal death. New markers emerge such as A Desintegrin And Metalloproteinase 12 (ADAM12), Placental Protein 13 (PP13) and Placental Growth Factor (PlGF), these have been associated with placental growth and development. Altered levels of these markers have been reported to be associated with chromosomal abnormalities, fetal growth restriction and maternal PE. For example, ADAM12 values were clearly reduced early in the first-trimester for all trisomies and PP13 and PlGF were reduced in early-onset PE. The search for new potential markers that are capable of detecting the presence of pathological conditions early in pregnancy with a high sensitivity and specificity is still a major challenge. Accurate prediction of these pathologies is crucial for prenatal diagnostic testing, for adequate monitoring of pregnancies at risk for hypertensive and other diseases and for the development of preventive treatment strategies to improve maternal and perinatal outcome. While screening for DS currently has a low uptake, it may be anticipated that a more generic approach to screening as “screening for fetal and maternal health”, may be more preferred by the pregnant women. We will then facilitate ‘a la carte’ screening, with pregnant women opting in for e.g. screening for preeclampsia or maternal health, trisomy 13 and 18, and may be choosing not to be informed about the DS risk, as a child with DS might be welcome in their family. This research has delivered some of the elements (screening for other pregnancy complications like trisomie 13 and 18, PE, macrosomia in gestational diabetes pregnancies) of such a new screening program.