ADAM12 and first trimester trisomy screening

Thesis event information

Date and time of the thesis defence

Place of the thesis defence

OYS, auditorium 4

Topic of the dissertation

ADAM12 and first trimester trisomy screening

Doctoral candidate

M.D. Yrtti Valinen

Faculty and unit

University of Oulu Graduate School, Faculty of Medicine, Medical Research Center Oulu

Subject of study

Obstetrics and gynaecology


Professor Seppo Heinonen, University of Helsinki


Professor Markku Ryynänen, University of Oulu

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ADAM12 and first trimester trisomy screening

The purpose of the study was to evaluate the efficacy of adding a new marker, a disintegrin and metalloproteinase domain 12 (ADAM12), in the first trimester screening programme for chromosomal disorders in singleton pregnancies in the general Finnish population. In combined first trimester screening, pregnancy associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotropin (fβ-hCG) are measured from maternal serum, and fetal nuchal translucency (NT) thickness is measured using ultrasound (US) during 8+0–13+6 weeks of gestation. After that a computerised risk calculation program is used to calculate an individual risk score for chromosomal disorders. This study investigated whether the detection rate (DR) would improve and the false positive rate (FPR) decrease after adding ADAM12 in the risk calculation program.
The screening of fetal chromosomal abnormalities is a part of modern maternity care in Finland. The decree issued by the Ministry of Social Affairs and Health states that every community in Finland should offer free-of-charge voluntary screening for chromosomal disorders during the first trimester as of 01/01/2010. The Ministry of Social Affairs and Health updated the decree on 01/01/2023. The main handicap in screening is the loss of healthy fetuses due to invasive procedures, chorionic villus sampling (CVS), or amniocentesis (AC). There are now some pilot projects for a noninvasive prenatal test (NIPT) as a primary screening test, which has the potential to reduce invasive procedures.
In this study, the combined first trimester screening for Down syndrome yielded a DR of 87.5% for a 4.9% FPR. Voluntary participants comprised 4 765 women and the number of Down syndrome cases was 24 (1:199). The percentage of women older than 35 years of age was 18.6%, the expected number in Finland.
Adding ADAM12 as a parameter in risk figure calculation for Down syndrome or other chromosomal abnormalities did not improve the screening performance; neither DR was improved nor FPR reduced. The main prerequisite for improving test performance is that the new marker is independent of the markers in use. However, there was a statistically significant correlation between the log MoMs of ADAM12 and PAPP-A, which may explain the limited ability of the new marker, ADAM12.
Last updated: 2.2.2024