The present study has 2 primary objectives: 1: The first aim of the present study is to explore early detection possibilities using plasma hemopexin activity and plasma ATP levels in cohorts of pregnant women in a time course manner (experiment 1).…
ID
Source
Brief title
Condition
- Maternal complications of pregnancy
- Vascular hypertensive disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Experiment 1: Blood samples (10 ml heparinised and 10 ml EDTA) of 135 pregnant
women at high risk for developing preeclampsia will be taken at weeks 10, 14,
18, 20 and 25, 30, 35 and 40 of pregnancy. We will measure plasma hemopexin
activity and plasma ATP levels as well as various inflammatory parameters.
Experiment 2: Blood samples (10 ml EDTA, 10 ml heparinised blood) will be taken
from women diagnosed with preeclampsia (ISSHP criteria). We will measure
activation of inflammatory cells and plasma concentrations of hemopexin, ATP,
inflammatory parameters and other factors suggested to be involved in the
pathogenesis of preeclampsia. In tissue biopsies we will measure endothelial
cell activation and dysfunction.
Secondary outcome
nvt
Background summary
Preeclampsia is the most serious complication of pregnancy in the western
world. The aetiology is unknown and the pathophysiology is relatively unknown.
It is generally assumed that generalized inflammation and endothelial cell
activation play a prominent role in the pathogenesis of preeclampsia. More
recently, various circulating factors, such as sFlt-1 and endoglin, have also
been suggested to be involved in the pathogenesis of preeclampsia.
Early recognition of the disease is crucial for better obstetric care of
pregnant women at risk and their unborn child. Moreover, early detection of the
disease may also lead to better insight into the pathogenesis of PE, which at
the moment is largely unknown. Finally early diagnosis may facilitate the
generation of novel therapeutic strategies.
We have recently shown that hemopexin activity, a heme-binding acute phase
protein with protease activity, is increased during normal pregnancy, but not
during preeclampsia. The decrease of hemopexin activity during preeclampsia is
due to increased plasma levels of ATP, a potent inhibitor of hemopexin
activity. This suggests that hemopexin activity plays a role in the normal
physiology of pregnancy, and that the decreased activity in preeclampsia is
involved in the pathogenesis of this disease.
Study objective
The present study has 2 primary objectives:
1: The first aim of the present study is to explore early detection
possibilities using plasma hemopexin activity and plasma ATP levels in cohorts
of pregnant women in a time course manner (experiment 1).
2: The second aim of the present project is to study plasma hemopexin activity
and ATP levels in the various forms of preeclampsia, early onset and late onset
preeclampsia as well as severe and mild form of PE. At the same time we will
investigate the relationship between plasma hemopexin and ATP with inflammatory
parameters and other circulating factors, which are suggested to play a role in
the pathogenesis of preeclampsia (experiment 2), in PE.
Study design
Experiment 1: a longitudinal observation study. Experiment 2: Observational
study.
Study burden and risks
If possible (i.e. during pregnancy and preeclampsia) blood samples will be
taken by means of extra blood samples during routine sampling in the hospital.
For non-pregnant women, 20 ml of blood will be taken at a suitable time point.
This will not pose any risk on the individuals.
Biopsies will be taken during caesarean section, performed as part of the
treatment of the women. Therefore this will also not be associated with any
risk for the patients.
Hanzeplein 1
9713 GZ
NL
Hanzeplein 1
9713 GZ
NL
Listed location countries
Age
Inclusion criteria
Experiment 1: Pregnant women who have been diagnosed to be at increased risk for developing preeclampsia, i.e. women who have been diagnosed with pre-existent hypertension, diabetes mellitus, vasculitis, renal disease, autoimmune disease, malignancy, or women with preeclampsia in their previous pregnancy, women carrying twins. ;Experiment 2:
Preeclamptic patients:
* Preeclampsia defined by the ISSHP criteria (see onderzoeksprotocol)
* Primigravid
* Age: >/<= 18 years and <40 years;Pregnant women who deliver preterm
* preterm delivery, i.e. before 36 weeks
* Age: >/<=18 years and <40 years;Pregnant women who deliver a growth restricted baby
* IUGR * Age: >/<=18 years and <40 years;Normal pregnant women:
* Primigravid
* Age: >/<= 18 years and <40 years;Control non-pregnant women :
* Healthy nulligravid women
* Age: >/<= 18 years and <40 years
Exclusion criteria
Experiment 1: pregnant women without an increased risk of developing preeclampsia;Experiment 2:
Preeclamptic women:
Diagnosis of pre-existent hypertension,
diabetes mellitus,
vasculitis,
renal disease,
autoimmune disease,
malignancy, ;Healthy pregnant women:
* Multiparity
* Multiple pregnancy
* Fetal growth retardation
* Other pregnancy complications
* Hypertension
* Any known chronical illnesses
* Age: <18 years and >40 years
* smoking;Control non-pregnant women:
* Multiparity
* Age: <18 years and >40 years
* Existence of any known diseases
* smoking;pregnant women with preterm delivery
Diagnosis of
Treated pre-existent hypertension,
diabetes mellitus,
vasculitis,
renal disease,
autoimmune disease,
malignancy,
signs of infection
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL25930.042.08 |