ADAM 12 en PP 13
Promising markers in the first trimester of pregnancy, concerning a elevated risk for Down syndrome and high risk pregnancies.

The first trimester combined test, to calculate the risk for Down syndrome is
composed of the maternal serum concentrations pregnancy-associated plasma
protein A (PAPP-A) and the free β subunit of human chorion gonadotrophin
(fβhCG), combined with the measurement of the nuchal translucency (NT). There
is a potential new marker, A Disintegrin And Metalloproteinase (ADAM12). ADAM12
is a glycoprotein which is synthesized by the placenta. The maternal serum
concentrations of ADAM12 are reduced in Down syndrome and Edwards syndrome
pregnancies. To make sure ADAM12 is a good screening parameter for the first
trimester, we want to determine the normal physiological concentrations of
ADAM12 during the first trimester.

Beside that there is another marker PP13. Placental Protein (PP13), a new
maternal serum marker, shows potential for early detection of pre-eclampsia.
Pre-eclampsia affects 2-7% of all pregnant women worldwide and is a major cause
of maternal, fetal and neonatal morbidity and mortality. PP13 is a protein
expressed only in the placenta. It is involved in gluing the placenta to the
uterus, and in remodelling the maternal arteries to expand them. Previous
studies suggest that the gene for PP13 is down regulated in women with
pre-eclampsia requiring that in pregnancies resulting in early pre-eclampsia
there is impaired placental functional responsiveness to PP13 during the first
trimester of pregnancy.

To determine the normal physiological concentrations of ADAM12 and PP13 during
the first trimester, venous blood samples will be taken from 100 pregnant women
at 6, 8, 10, 12 weeks of gestation and from 100 different pregnant women at 7,
9, 11, 13 weeks. The ADAM12 concentrations will be determined and the serum
will be stored. From 50 women capillary blood samples will also be taken. These
samples will be stored at 25 degrees and 40 degrees Celsius on filter paper
(bloodspots) and in regular test tubes. The analysis of those concentrations
will show the stability of ADAM12 and PP13 and any differences in ADAM12 and
PP13 concentrations in venous vs. capillary blood.

1- To determine the physiological concentrations of ADAM12 and PP13,
longitudinal, in the early first trimester in normal pregnancies.

2- To analyse the stability of these proteins, the effect of transport and
higher temperatures.

3- To compare the concentrations form the bloodspots vs venous blood.

4- Creating a serum-bank / data-bank from normal healty pregnancies, what can
be used in the future to receive normal concentrations for new markers.

5- Compare the differences in concentrations of the markers between normal
pregnancies and pregnancies after IVF, women with diabetes or pregnant women
with a history of preterm labour, foetal growth restriction or pre-eclampsia.

6- To determine the relation between different levels of the serum markers and
adverse outcome of the pregnancy.

observational study

Pregnant women visit the hospital 4 times, they undergo venous blood sampling
and a short ultrasound examination of the mother. Venous blood sampling and
ultrasound examination is not associated with any risks.