Identifying placental disease during pregnancy using cfDNA of placental cells in the maternal circulation to discover new therapeutic placental targets for fetal treatment.
ID
Source
Brief title
Condition
- Placental, amniotic and cavity disorders (excl haemorrhages)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To determine the methylation profiles of placental cell populations of:
- uncomplicated pregnancies (controls).
- inflammation in the placenta (cases).
Secondary outcome
- Identify underlying genes or genetic pathways related to identified
methylation placental profiles of involved in (ab)normal placental development.
- Define placental markers that can predict an abnormal inflamed placenta
(chorioamnionitis and intervillositis).
Background summary
So far, it is only possible to assess placental abnormalities after birth with
histological analysis. To treat placental abnormalities during pregnancy, it is
important to recognize placental abnormalities as early as possible, before
birth. The 2 most common inflammatory placental abnormalities that cause poor
pregnancy outcomes are chorioamnionitis and intervillositis. Fragments of the
placenta are known to be present in the mother's blood (cfDNA). With a new
technique; Methylation sequencing (MeD-seq) we are going to identify for the
first time the DNA profiles of these placenta fragments in the mother's blood
(cfDNA). With this pilot study, we aim to investigate the most common
inflammatory placental abnormalities that cause poor pregnancy outcomes such as
fetal distress, asphyxia and (intra uterine) death. This will be the first
prenatal test to recognize inflammatory placental damage. This will allow us in
the future to assess the placenta earlier, during pregnancy without harming the
baby.
Study objective
Identifying placental disease during pregnancy using cfDNA of placental cells
in the maternal circulation to discover new therapeutic placental targets for
fetal treatment.
Study design
A single center prospective observational pilot cohort study will be at one
timepoint at delivery of the baby/placenta at the Erasmus MC.
Study burden and risks
No experimental medication will be used. Women will be treated according to
local hospital protocol. No additional risks or burden are expected from the
study.
Risks for obtaining maternal blood: For all 30 cases, the risks involve
primarily the burden of participating in a study. For this study we need 20 ml
blood which will be collected during the regular venapunction in the hours
before labour needed for clinical parameters. There will be no extra hospital
visit or no extra time point of the venapunction. Participants will not undergo
any additional procedures. However, the blooddrawing will take extra time as 4
vials (total 20 ml) will be needed for this study. The risks of participation
are considered to be very low.
Risks for placental sample: No site visits, no participation of patients
required. No treatment. The placentas of the patients are always stored for
clinical analysis. If patients are willing to give consent this tissue can be
used for future research. We use material from the pathology archive that can
be used for research. There is an opt-out regulation with a database. For every
sample the pathology department checks if the patient has given permission for
using their tissue for research.
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Listed location countries
Age
Inclusion criteria
General:
- Pregnant women >= 18 years and <= 45 years who are willing to participate.
- Sufficient understanding of Dutch in speaking and reading.
- Willingness to give written informed consent.
- Singleton pregnancy.
- Blood drawing (venapunction) planned for clinical purposes.
Two patient groups are eligible:
- Healthy pregnant women with an uncomplicated pregnancy (10 controls).
- Healthy pregnant women with a premature delivery (between 24 and <37 weeks)
clinically with suspicion of inflammation (20 cases).
Placentas from the pathology archive that can be used for research for a
baseline quality check:
- 10 placentas from an uncomplicated pregnancy (controls)
- 10 placentas with a premature delivery (between 24 and <37 weeks) clinically
with suspicion of inflammation (cases)
Exclusion criteria
Multiple pregnancy.
- Gastro-intestinal diseases, heart diseases, liver, pancreas and kidney
diseases.
- Pre-existent diabetes mellitus.
- Unable or unwilling to give informed consent.
- Fetus with a known congenital/chromosomal abnormality.
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 | NL86223.078.24 |