Objective: In this project we, as a collaborative network of Netherlands academic hospitals from Utrecht, Amsterdam, Rotterdam, Leiden and Groningen, propose to further optimize and validate MG-NIPD at early stages (week 8-10) of pregnancy, in order…
ID
Source
Brief title
Condition
- Congenital and hereditary disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main study parameters/endpoints: Percentage of concordant results between
MG-NIPD performed early in pregnancy and PND (or postnatal cord blood) carried
out at a later stage, percentage of tests yielding inheritance predictions with
>99% confidence (Part I), and patients* and professionals* perspectives on NIPD
(Part II).
Ad. Part I: The statistics behind MG-NIPD were established with Dr. Gerard te
Meerman (UMCG) and have been described in detail in our publication (Vermeulen
et al., 2017). In this study, MG-NIPD predictions for 100-120 different risk
pregnancies will be compared to the PND (or cord blood) measured genotype of
the fetus. We will report how often MG-NIPD correctly predicted the actual
genotype of the fetus, how often the test was inconclusive and how often the
wrong prediction was made (as mentioned, we expect this to not happen). We will
also report the confidence levels of our predictions (which we aim to always be
>99%). Based on these performance parameters, the to be determined exact costs
of the test and the turn-around time of results (MG-NIPD can be completed
within one week, possibly faster), clinics should individually decide whether
or not they wish to offer MG-NIPD to risk couples carrying a monogenic disease.
Ad. Part II: We will analyse the interview data according to principles of
constant comparison. Along this path of analysis, initial *open
coding* (initial codes given to fragments of text) will be replaced by *axial
coding* (description and integration of codes). In the final phase of
*selective coding*, core concepts will be determined and the relationships
between important categories will be tested and interpreted.
For the survey data descriptive analyses will be used. For any comparison,
chi-squared test will be used for categorical data and t-tests for continuous
data.
Secondary outcome
not applicable
Background summary
Our current health care system offers various prenatal genetic tests to future
parents and pregnant women who wish to be informed whether their unborn child
is affected with a severe genetic disease. In case of monogenic disorders such
as cystic fibrosis, thalassemia, Duchenne muscular dystrophy, etc, pregnant
couples at risk currently rely on chorionic villus sampling or amniocentesis;
two invasive prenatal diagnostics (PND) procedures that both carry a small
procedure-related risk of miscarriage. Their invasive character and associated
risk of losing a healthy pregnancy are perceived as highly burdensome by the
pregnant women. Couples may also opt for pre-implantation genetic diagnostics
(PGD), which offers the possibility to select embryos without the genetic
disorder, which are then transferred into the uterus. However, PGD treatment
also imposes a burden because of the intensive and long treatment, medication
side effects and complications of the ovary stimulation. After PGD, there is a
small residual risk of ~2% of misdiagnosis. Because of this residual risk, PND
is offered to these couples for reassurance, but often declined because of the
miscarriage risk.
In recent years, a major advance in prenatal testing has been the delivery of a
safer, earlier and more accurate non-invasive prenatal test (NIPT) aiming at
aneuploidy such as Down syndrome. NIPT has resulted in a significant reduction
in invasive testing, but is still a screening test that requires confirmation
by invasive testing. Moreover, NIPT can only identify large chromosomal
abnormalities, not the subtle genetic variation that typically underlies
monogenetic disorders such as cystic fibrosis, thalassemia, etc. For this
diverse category of disorders, we recently developed a revolutionary new test
called Monogenic Non-Invasive Prenatal Diagnosis (MG-NIPD). As we published,
MG-NIPD only requires a simple blood draw from both parents to determine with
high confidence, high sensitivity and in a cost-efficient manner the
disease/carrier status of the fetus early during pregnancy.
Study objective
Objective: In this project we, as a collaborative network of Netherlands
academic hospitals from Utrecht, Amsterdam, Rotterdam, Leiden and Groningen,
propose to further optimize and validate MG-NIPD at early stages (week 8-10) of
pregnancy, in order to be able to clinically implement the test (Part I:
Validation study). Moreover, we will explore patient and health professional
perspectives on MG-NIPD (Part II: Patients and Professional perspectives
study).
Study design
Part I: Prospective parallel study design with 100-120 couples.
Part II: Mixed methods approach using qualitative and quantitative research
methods.
Study burden and risks
The study involves the comparison of two diagnostic prenatal tests; invasive
testing (PND) and MG-NIPD (Study Part I). Outcomes of the MG-NIPD are not given
to the participants. The study will also be blinded for both the laboratory
specialists involved in MG-NIPD/PND and the clinicians involved in the PND.
Participating couples (both partners) are asked to donate one blood sample
before testing (preferably before pregnancy). Subsequently, women are asked to
donate a second blood sample in early pregnancy. Whenever possible, this blood
draw will be combined with the regular blood draw in pregnant women. Follow-up
and postnatal assessment of the health of the child (presence of the disorder)
is already included in the standard care. The participants are asked for
permission to use left-over DNA from routine PND (or postnatal genotyping on
cord blood) for more detailed genetic analysis of the disease locus of the
fetus, necessary for detailed evaluation of MG-NIPD accuracy and performance.
No risks or discomfort, other than drawing blood, is expected for study
participants.
To explore couples* perspectives, preferences and needs towards MG-NIPD (Study
Part II), couples potentially eligible for MG-NIPD will be asked to participate
in one 45-min. semi-structured interview(s) or to complete (a)
questionnaire(s).
Uppsalalaan 8
Utrecht 3584CT
NL
Uppsalalaan 8
Utrecht 3584CT
NL
Listed location countries
Age
Inclusion criteria
* Pregnant couples (or couples planning a pregnancy) at increased risk (25%) of carrying a child with one of the following severe monogenic recessive diseases (thalassemia, sickle cell anemia, cystic fibrosis, hemophilia, Spinal Muscular Dystrophy, Duchenne or one of the serious recessive diseases present in a genetically isolated population) AND opting for PND (or postnatal cord blood).
OR
* Pregnant couples (or couples planning a pregnancy) from a genetically isolated population with one partner carrier of a severe recessive disease (+/-couples).
Exclusion criteria
* Multiple gestation/vanished twin/empty sac(s) detected at any time before blood sampling during pregnancy
* Maternal age <18 years
* Insufficient knowledge of Dutch or English language or impossibility to understand the study purpose.
* Women carrier of an X-linked recessive disorder and pregnant of a girl.
* Gestational age > 14 weeks
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 | NL66219.041.18 |