The primary objective of this study is to investigate how the vascular regulation is altered in the maternal as well as placental vasculature of women with pregnancy disorders (preeclampsia, pregnancy-induced hypertension, FGR, preterm birth,…
ID
Source
Brief title
Condition
- Pregnancy, labour, delivery and postpartum conditions
- Vascular hypertensive disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The vascular reactivity of arteries from omental tissue, subcutaneous fat and
placental tissue will be studied using 1) wire myography to assess vascular
contractions and relaxations to agonists, as well as the effects of antagonists
on these contractions and relaxations, 2) pressure myography to assess vascular
distensibility and flow-mediated vasodilation, 3) biomarker concentrations in
maternal and umbilical cord blood, 4) molecular response of placental and
vascular cell types.
Secondary outcome
- To determine if and how alterations in maternal vascular reactivity correlate
with alterations in foetoplacental vascular reactivity.
- To examine whether (novel) therapeutics can restore this altered response.
- To determine if and how alterations in maternal and placental vascular
reactivity correlate with biomarker concentrations in maternal blood an
umbilical cord blood.
- To detect placental alterations at the tissue level and at the molecular
level for different cell types contributing to the maternal-placental
interface.
Background summary
Normal pregnancy necessitates a large increase in blood flow to the
fetoplacental unit, which is achieved through tremendous adaptations of the
maternal cardiovascular system. Abnormal maternal vascular adaptations and
subsequent reduced placental perfusion in early gestation play a significant
role in the development of maternal vascular complications of pregnancy, and
can indirectly lead to chronic disease in later life.
Vascular changes have been observed in pregnant women with preeclampsia, fetal
growth restriction (FGR), preterm birth, and diabetes mellitus. Placental and
vascular function are thus crucial determinants for pregnancy outcome, fetal
health and neonatal outcome. As the placenta is composed of a maternal and a
fetal circulation, sufficient placental function is determined by adequate
function of both vasculatures. However, many pregnancy disorders remain
incurable to date as the exact mechanisms that contribute to the vascular
changes in pregnancy disorders remain poorly understood.
The identification of such alterations and the underlying mechanisms is
necessary to provide novel therapeutic insights for these pregnancy disorders.
We therefore aim to examine how maternal and fetoplacental vascular reactivity
are altered pregnant women that suffer from vascular dysfunction. By collecting
small pieces of omental tissue and subcutaneous fat tissue, as well as the
placenta from the same women that will undergo an elective (or emergency)
caesarean section, we will be able to study vascular function in all these
tissues. These experiments will provide a unique opportunity to study
(patho)physiological processes with human tissues that have high translational
value to the clinic and reduce the need for animal research, without exposing
the women to significant risks.
The importance of this study is that it may identify new medications that could
be used to treat pregnancy complications, and thereby improve the outcomes of
pregnant women and their fetuses.
Study objective
The primary objective of this study is to investigate how the vascular
regulation is altered in the maternal as well as placental vasculature of women
with pregnancy disorders (preeclampsia, pregnancy-induced hypertension, FGR,
preterm birth, obesity, dysbiotic microbiome, and diabetes). If alterations are
identified, the secondary objectives are to examine whether novel therapeutics
can restore this altered response and to determine how these alterations
correlate with biomarker levels in maternal and umbilical cord blood, and
placental alterations at molecular and cell level.
Study design
Cross-sectional ex vivo research, conducted at the Erasmus MC University
Medical Center Rotterdam. As no intervention is involved, this study can be
considered as an observational study with a minimally invasive one-off
procedure for each patient.
Study burden and risks
We expect no (or minimal) risks associated with participation. For the
placental and biomarker studies we will only use waste material (placenta,
maternal blood and umbilical cord blood), so there is no additional risk in
collecting it. For the maternal vascular studies, the removal of the pieces of
subcutaneous fat tissue and omental tissue (of approximately 1.5 x 1.5 cm each)
after incision will not be noticed by the subject, not in a negative sense nor
in a positive sense. The only minor risk associated with the removal of a piece
of omental tissue is bleeding in case the tissue is not tied off completely.
Collection of the tissues will not complicate the care or recovery of the
patients, and will not interfere with the delivery of the baby. Nor will it
cause problems for further pregnancies.
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in this study, a control subject must
meet all of the following criteria:
- Pregnant persons >= 18 years old
- Sufficient command of the Dutch or English language
- Willing to donate a small sample of subcutaneous fat tissue and omental tissue
- Willing to provide written informed consent
- Undergoing elective caesarean section
- Blood pressures in a relatively normal range, which is 90-140
(systolic)/60-90 (diastolic).
In order to be eligible to participate in this study, a study subject must meet
all of the following criteria:
- Women >= 18 years old
- Sufficient command of the Dutch or English language
- Willing to donate a small sample of subcutaneous fat tissue and omental tissue
- Willing to provide written informed consent
- Undergoing elective or emergency caesarean section
- Clinically diagnosed with either one of the following conditions:
preeclampsia, FGR, preterm birth, obesity, dysbiotic microbiome, and diabetes
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
- Admission to an Intensive Care Unit (ICU) for any reason
- Admission during an obstetric emergency (Control group only)
- A viral infection (SARS-CoV-2 only during the third trimester)
- Severe fetal congenital anomalies
- Placenta praevia, placenta accreta/increta.
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 | NL82454.078.22 |