The primary objective of this study is to determine the ability to diagnose (in a clinical validation study) the health of the early foetus by using the non-invasive nanoCAGE RNA-sequencing test using circulating cell-free RNA isolated from first…
ID
Source
Brief title
Condition
- Maternal complications of pregnancy
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint of this study is the predictive accuracy of the nanoCAGE
RNA-seq test for fetal and maternal well-being. Fetal well-being is monitored
by intra-uterine growth restriction and preterm birth; maternal well-being is
monitored by clinical symptoms of pre-eclampsia (new-onset hypertension during
pregnancy with proteinuria) and related syndromes (HELLP syndrome).
Secondary outcome
The secondary endpoint is the discriminative power of the nanoCAGE RNA-seq test
(proof-of-principle study) for the success of implantation rate and
pathophysiological insight in early miscarriage using RNA isolated from the
culture medium of human pre-implantation embryos (blastocyst stage).
Background summary
Circulating cell-free DNA isolated from maternal plasma during the first
trimester of pregnant women has revolutionized non-invasive prenatal
diagnostics. This approach, known as NIPT (Non-invasive prenatal trisomy test),
is currently being implemented in the Netherlands.
Likewise, it can be assumed that the same approach, massively parallel
sequencing, when applied on circulating RNA (instead of DNA) can be used for
non-invasive prenatal diagnosis of pregnancy-associated diseases with a
placental origin, such as pre-eclampsia, intra-uterine growth restriction and
the HELLP syndrome. This project aims to accomplish this at the presymptomatic
stage.
Study objective
The primary objective of this study is to determine the ability to diagnose (in
a clinical validation study) the health of the early foetus by using the
non-invasive nanoCAGE RNA-sequencing test using circulating cell-free RNA
isolated from first trimester plasma of a broad population of pregnant women.
The RNA-seq data will be correlated to pregnancy outcome (pre-eclampsia,
intra-uterine growth restriction, preterm birth).
Study design
Pregnant women (week 9-14) (n =2000) attending the Prenatal Units of three
centers (AMC, VUMC and OLVG -location East) will be asked for a blood sample
(EDTA blood) following informed consent. Plasma will be retrieved by
double-centrifugation, cell-free RNA isolated using an automated system
(QIAsymphony) and used for cDNA library construction using an in-house method.
Samples will be prescreened by Taqman PCR with a marker set. Libraries from
patients at risk for pregnancy complications (pre-eclampsia, IUGR, HELLP) will
be selected, and subjected to massively parallel sequencing on a HiSeq 2500
system. Healthy, non-pregnant women will be included as an extra control group
to help determine the fetal RNA fraction in maternal plasma.
Study burden and risks
Minimal (single blood withdrawal)
De Boelelaan 1117
Amsterdam 1081HV
NL
De Boelelaan 1117
Amsterdam 1081HV
NL
Listed location countries
Age
Inclusion criteria
Age 18 years or older at enrollment,
Clinically confirmed pregnancy,
Gestational age between 9-14 weeks,
Pregnancy records accessible and available for data collection exam,
Able to provide consent for participation using language appropriate forms.
Exclusion criteria
Invasive prenatal procedure (amniocentesis or CVS) performed within 2 weeks prior to enrollment,
Twin pregnancy,
Vanishing twin.
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 | NL48929.029.14 |