Normal fetal neurodevelopment: healthy control population to compare with fetuses with a congenital heart disease

Congenital heart disease (CHD) is the most prevalent congenital anomaly and
accounts for significant (neonatal) mortality and morbidity. Not only
cardiovascular and surgical problems can arise, also a high percentage of CHD
children suffer from neurodevelopmental disorders. Recent studies have
indicated that some of these neurodevelopmental disorders are already present
at birth. However, the precise intrauterine pathophysiology is not known. The
current study is designed to analyse the normal fetal neurodevelopment and to
collect biomaterial of healthy fetuses for the LUMC Biobank Verloskunde, to
serve as a control group for fetuses with congenital heart defects. In the
department of fetal medicine of the LUMC, all consecutive CHD fetuses are
systematically included in a fetal neurodevelopmental surveillance program
(Heart And NeuroDevelopmental Program). Data and biomaterial of fetuses with
CHD are stored in the LUMC Biobank Verloskunde.

1.To explore the intrauterine cerebral development by ultrasound in healthy
fetuses to compare to the findings in fetuses with severe CHD. We want to do
this by establishing benchmark values in healthy control fetuses, to compare
these with our cohort of fetuses with severe CHD, with regard to 1) brain
development, 2) growth trajectories of brain structures, 3) brain perfusion and
4) brain volume.
2. To collect and store placentas and biomaterial of the umbilical cord of
healthy control fetuses in our LUMC Biobank congenital heart disease for future
research.

Single-center, prospective, observational cohort study in het LUMC.

Prenatal ultrasound provides no risk to the mother and/or fetus as ultrasound
is a safe and non-invasive technique.

Burden and risks associated with participation are:
- Risk of unexpected ultrasound findings. However, the chance of encountering a
fetal abnormality is very low (<<1%), as all the subjects had a
normal second trimester structural anomaly scan before inclusion as
part of the national screening program.
- Extra time effort (maximum 5 times 20 minutes)
- In some cases, transvaginal scanning is required, which can be burdensome for
some women. Transvaginal ultrasound can be refused by the
subjects at any time. As transvaginal scanning is done often in the
first trimester for establishing the due date, most women are familiar with the
transvaginal ultrasound.

Subjects do not directly benefit from this study. The results of this study
will possibly benefit other fetuses/children and their families by creating new
knowledge. Insight in normal development of the brain will aid future patients
(for example fetuses with CHD or brain abnormalities). By identifying detailed
information about timing and mechanism of brain injury in patients with severe
CHD, care can be further optimized, neuroprotection programmes can be
developed, and appropriate treatment and support for the individual patients
can start as early as possible to improve quality of life and possibly reduce
costs of developmental impairments.