Primary objective:To investigate whether there are differences in DV flow measured during the 13-week GUO between pregnancies complicated by UPI and pregnancies not complicated by UPI.Secondary objectives:(1) To investigate whether there are…
ID
Source
Brief title
Condition
- Placental, amniotic and cavity disorders (excl haemorrhages)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Difference in DV flow measured during the 13-week GUO between pregnancies
complicated by UPI and pregnancies not complicated by UPI.
Secondary outcome
(1) Difference in uteroplacental Doppler parameters measured during the 13-week
GUO between pregnancies complicated by UPI and pregnancies not complicated by
UPI.
(2) Explorative biomarker analyses in 13- and 32-week blood samples in
pregnancies complicated by UPI and pregnancies not complicated by UPI.
Background summary
Important pregnancy complications, such as preeclampsia (PE) and fetal growth
restriction (FGR) share uteroplacental insufficiency (UPI) as a common
pathophysiology. PE and FGR represent a major concern in care for pregnant
women and are a leading cause of perinatal morbidity and mortality.(1) For UPI
and its subsequent pregnancy conditions, no causal treatment is available,
besides adequate fetal monitoring and timely delivery.
Our research group retrospectively demonstrated that the pulsatility index (PI)
in the ductus venosus* (DV) measured in the first trimester is elevated in
fetuses who later became growth restricted due to UPI (data not published yet).
At clinical presentation,UPI is also reflected in the resistance to blood flow
in uteroplacental arteries (aa. uterinae and a. umbilicalis). It is unknown
whether these changes are already present in the first trimester. Prospectively
evaluating DV flow in the first trimester between pregnancies complicated by
UPI and pregnancies not complicated by UPI is needed to validate our
observation, and is also needed to investigate whether there are already
differences in uteroplacental ultrasound (US) Doppler parameters between these
populations. Possibly, the risk for UPI and its high-impact pregnancy
complications can be estimated in the first trimester based on US. This is
especially interesting concerning pregnancies with a late onset (>=32 weeks of
pregnancy) of FGR (as a consequence of UPI) since the accuracy of this
diagnosis is poor.
Literature demonstrates that implementing well-known biomarkers (PlGF and
soluble fms-like tyrosine kinase-1) in a first trimester screening algorithm
for FGR (as a consequence of UPI) substantially improves detection rates.(2)
However, it has not been investigated to what extent these biomarkers - next to
newly developed, promising biomarkers following array studies - contribute to
the accuracy of a first trimester screening strategy based on DV flow and
possibly uteroplacental Doppler parameters.
We aim to investigate whether there are already differences during 13-week
GUO** in DV flow and possibly uteroplacental Doppler parameters between
pregnancies complicated by UPI and pregnancies not complicated by UPI***.
Additionally, we want to study first trimester levels of known- and newly
developed, promising UPI related biomarkers exploratively between these
populations; eventually evaluating to what extent biomarkers possibly
contribute to the accuracy of first trimester US based prediction of UPI that
develops later in pregnancy. To comment on the most optimal moment for
biomarker analyses, we will also collect blood samples during the extra US at
32 weeks* gestation.
Prospectively evaluating this in the first trimester of pregnancy might be a
stepping stone towards a 1st trimester screening strategy for UPI based on
Doppler parameters and possibly biomarkers. Such a newly to develop screening
algorithm would allow clinicians to make a risk assessment, early in pregnancy
with the possibility of intervening by means of antiplatelet agents or
intensified fetal monitoring; this might prevent or milden the consequences of
UPI. Clarifying the additional value of aforementioned first trimester
screening strategy could become very valuable, since a 13-week SEO might become
part of standard prenatal care.
*The ductus venosus is a shunt between the placental umbilical vein and fetal
inferior vena cava.
**In contrast to the 13-week SEO (that is in Dutch: structureel echoscopisch
onderzoek, SEO) - which is offered in research setting from September 2021 -
there are specific indications for a 13-week GUO (that is in Dutch: geavanceerd
ultrageluidsonderzoek, GUO: for indications see section D4). The 13-week GUO is
in the context of prenatal diagnostics and falls under the scope of the
prenatal care centers.
***UPI is defined as abnormal Doppler parameters in combination with deflection
of the growth curve.(3) At the visit for the 13-week GUO, it is unknown if a
pregnancy will be complicated by UPI or not. To evaluate whether UPI develops
during pregnancy, Doppler parameters
and fetal growth will be evaluated 2 times during the pregnancy: during the
20-week SEO and during an extra ultrasound >=32 weeks* gestation (merely in the
context of the study). To confirm UPI postnatally, the umbilical cord,
placental disk and membranes will be collected after delivery and examined for
severe maternal vascular malperfusion (MVM) lesions according to the Amsterdam
consensus group criteria. (4)
Consent to access the participants* medical file will be asked in order to
include data on the course of the pregnancy and delivery in the study.
Participation in the study is completed as soon as the participant has given
birth and the umbilical cord, placental disk and membranes are collected.
References:
(1) Youssef L, Miranda J, Paules C, Garcia-Otero L, Vellvé K, Kalapotharakos G,
et al. Fetal cardiac remodeling and dysfunction is associated with both
preeclampsia and fetal growth restriction. Am J Obstet Gynecol [Internet].
2020;222(1):79.e1-79.e9.
(2) Crovetto F, Triunfo S, Crispi F, Rodriguez-Sureda V, Dominguez C, Figueras
F, et al. Differential performance of first-trimester screening in predicting
small-for-gestational-age neonate or fetal growth restriction. Ultrasound
Obstet Gynecol. 2017;49(3):349-56.
(3) Gordijn SJ, Beune IM, Thilaganathan B, Papageorghiou A, Baschat AA, Baker
PN, et al. Consensus definition of fetal growth restriction: a Delphi
procedure. Ultrasound Obstet Gynecol. 2016.
(4) Khong TY, Mooney EE, Ariel I, Balmus NCM, Boyd TK, Brundler MA, et al.
Sampling and definitions of placental lesions Amsterdam placental workshop
group consensus statement. Arch Pathol Lab Med. 2016;140(7):698-713.
Study objective
Primary objective:
To investigate whether there are differences in DV flow measured during the
13-week GUO between pregnancies complicated by UPI and pregnancies not
complicated by UPI.
Secondary objectives:
(1) To investigate whether there are differences in uteroplacental Doppler
parameters measured during the 13-week GUO between pregnancies complicated by
UPI and pregnancies not complicated by UPI;
(2) To exploratively study first and third trimester levels of known and newly
developed UPI related biomarkers between pregnancies complicated by UPI and
pregnancies not complicated by UPI; eventually evaluating to what extent
biomarkers contribute to the accuracy of first trimester US based prediction of
UPI.
Study design
Observational prospective study.
Study burden and risks
The study population consists of singleton pregnant women with an indication
for a 13-week GUO (for indications see section D4) in the UMCG. The 13-week GUO
includes measurements on DV flow and uteroplacental Doppler parameters; in the
context of the study we ask permission of the participant for including these
data in the research database, analyzing the recorded data and an extra blood
withdrawal (EDTA- and serumsample, 2 x 10 ml) for the explorative
biomarkeranalyses.
UPI is defined as abnormal Doppler profiles in combination with deflection of
the growth curve. At the visit for the 13-week GUO, it is unknown if a
pregnancy will be complicated by UPI or not. To evaluate whether UPI develops
during pregnancy, Doppler profiles and fetal growth will be evaluated 2 times
during the pregnancy:
- During the 20-week SEO (that is in Dutch: structureel echoscopisch onderzoek,
SEO).
- During an extra US at >=32 weeks* gestation. During the visit for this scan,
again an EDTA- and serumsample (2x10 ml) will be taken for biomarkeranalyses.
The 20-week SEO is part of standard prenatal care in the Netherlands and
includes measurements on Doppler parameters and fetal growth. A separate visit
is not necessary; in the context of the study we ask permission of the
participant for including these data in the research database and analyzing the
recorded data.
The extra US at >=32 weeks* gestation is merely in the context of the study. A
separate visit of circa 15 minutes is necessary but can easily be combined with
a routine prenatal care visit. In general, pregnant women are very much in
favour of an extra US investigation.
To confirm UPI postnatally, the umbilical cord, placental disk and membranes
will be collected after delivery and examined for severe maternal vascular
malperfusion (MVM) lesions according to the Amsterdam consensus group criteria.
(1)
Consent to access the participants* medical file will be asked in order to
include data on the course of the pregnancy and delivery in the study.
Participation in the study is completed as soon as the participant has given
birth and the umbilical cord, placental disk and membranes are collected.
References:
(1) Khong TY, Mooney EE, Ariel I, Balmus NCM, Boyd TK, Brundler MA, et al.
Sampling and definitions of placental lesions Amsterdam placental workshop
group consensus statement. Arch Pathol Lab Med. 2016;140(7):698-713.
Hanzeplein 1
Groningen 9700 RB
NL
Hanzeplein 1
Groningen 9700 RB
NL
Listed location countries
Inclusion criteria
Singleton pregnant women referred to the UMCG for an indicated 13-week advanced
anomaly scan (that is in Dutch: geavanceerd ultrageluidsonderzoek, GUO) will be
included.
Indications for a 13-week GUO are:
- A first degree relative of the fetus, two second degree relatives of the
fetus or other, further relatives with a comparable abnormality in the same
bloodline are eligible for a 13-week GUO if the abnormality is expected to be
visible at the 13-week GUO, that is: anencephaly, abdominal wall defect, spina
bifida, megacystis, certain limb defects, holoprosencephaly, body stalk
anomaly, diaphragmatic hernia, some congenital heart defects or use of
teratogenic medication of the mother which can cause visible abnormalities in
the first trimester;
- Monochorionic twin pregnancy or larger multiple pregnancy;
- Women with a burdened obstetric history, that is: with previous abnormalities
of the fetus/child, perinatal death or termination of pregnancy.
Exclusion criteria
Age <18 years;
Chromosomal abnormalities;
Fetal demise during pregnancy, not caused by uteroplacental insufficiency;
Termination of pregnancy;
Congenital anomalies;
Suspected/proven infections;
Pregnant women who are unable to reasonably assess their interests in
participating in the study.
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 | NL79004.042.22 |