Selective fetal growth restriction in monoChOrioNic Twins - an inteRnAtional inveSTigation

Optimal diagnostic management and underlying pathophysiological mechanisms of
selective fetal growth restriction (sFGR) in monochorionic diamniotic (MCDA)
twin pregnancies have not been fully clarified.

The current diagnostic classification system based on three different umbilical
artery flow patterns has no increasing scale of severity and the predictive
value is limited. Since there is no treatment available for sFGR, predicting
fetal deterioration is key in preventing single or double demise. Outcome
prediction is furthermore important in the selection of cases that will be
offered selective reduction (to provide the larger twin with better prospects),
as well as determining monitor frequency and possible hospital admission. As
outcome prediction is clinically challenging, patient counselling is too, and
parents often encounter a great deal of uncertainty during the pregnancy.

Furthermore, little is known about the neurological development of sFGR
children (both antenatally and postpartum). Moreover, the psychological impact
of an sFGR pregnancy of the future parent)s) has not been studied before. The
impact of these factors should be taken into account during patient counseling,
which is currently not the case.

By our knowledge, this is the first international, multicenter, prospective
cohort study on sFGR.

Primary objective:
To improve outcome prediction in sFGR by developing a prediction model at the
time of sFGR diagnosis and by evaluating specific ultrasound parameters
throughout the pregnancy.

Secondary objectives:
- To increase our knowledge of the pathophysiology of sFGR in MCDA twins by
performing unique histological examinations of the sFGR placentas.
- To document perinatal morbidity and mortality after sFGR.
- To examine the fetal brain development and infant neurodevelopmental outcome
of until 2 years of age after a sFGR pregnancy.
- To assess the psychological impact on mental health of both
parents/caregivers (if applicable) during sFGR pregnancy and postpartum.

The design is a prospective multicenter international cohort study, in which
the Leiden University Medical Centre (LUMC), the University Hospital in Leuven
(UZ Leuven), the Karolinska University Hospital in Stockholm, BCNatal
(Barcelona), Mount Sinai Hospital (together with the Hospital for Sick
Children, both in Toronto), and the Boston Children's Hospital (Boston)
collaborate.

MCDA twins are at substantial risk of experiencing adverse prenatal conditions,
of which sFGR is one of them. The LUMC, UZ Leuven, the Karolinska University
Hospital and the BCNatal are all national referral centers with extensive
experience in managing complicated twin pregnancies. As sFGR is a rare
condition, it can be best studies through multicenter collaboration.

Most assessments of this study will be integrated as part of clinical care for
the sFGR twins. They will also be studied in our unselected cohort of MCDA
twins.
Antenatal, a burden for the pregnant mother during routine ultrasound might be
a prolonged examination time (+/- 10-30 minutes) for the additional
measurements, which can occur a maximum of 5 times. A clinical fetal MRI will
be performed between 28-32 weeks and require up to 60 minutes to complete. MRI
is considered a low-risk and minimally invasive procedure.

The questionnaires filled out by the parents will cost +/- 10-20 minutes of
their time (per questionnaire, per parent), with a total of 9 questionnaires
(prenatally and postpartum). After birth, the placenta will be examined
extensively. Neurodevelopmental evaluation at 2 years of age comprises both
filling out a questionnaire by the parents (which typically takes 30 minutes
per parent) and a neurodevelopmental assessment for some of the twin(s). This
assessment is generally experienced as enjoyable for children and are not
associated with any risk with a minimal burden (e.g. 120 minutes).

The burden for (some of) the child / children will be in the form of a
neurological examination to test cognitive and motor development (Bayley-III).
This is generally experiences as joyful by the children. The Bayley-III is not
associated with any risks, widely used, and takes +- 120 minutes to complete.
The Bayley-III is already part of standard follow-up in the Netherlands for
some indications (for example birth < 30 weeks or a birth weight < 1500 grams).
Not all the children will undergo the Bayley-III, for a list of indications
see: chapter 5.3 (Study procedures).