Introduction
Marfan Syndrome (MFS) is an inherited disorder of connective tissue with
multisystem involvement1 and a reported prevalence of
6.5 per 100.000.2 Mutations in FBN1 are found in more
than 90% of MFS cases.3 FBN1 encodes the
extracellular matrix protein fibrillin-1 which contributes to the
integrity and function of connective tissue.4 The
inheritance is autosomal dominant with a high penetrance and great
clinical variability.5
MFS is associated with increased morbidity and mortality primarily due
to progressive aortic dilatation, dissection and
ruptures.6, 7
Pregnancy with the physiological cardiac stress (increased stroke
volume, cardiac output and heart rate) 8, 9 remains a
controversial topic in MFS. Several studies regarding pregnancy related
cardiovascular complications in MFS have been conducted and data
collated in a systemic review from 2017.10 In this
study, aortic dissection rate was 7.9% and the mortality rate 1.2%
with a trend towards dissection occurring at pre-pregnancy aortic root
diameter above 40 mm (p=0.0504). Until a recent UK multicentre study
reported an aortic dissection of 1.9% in 221 live
births,11 most studies have been rather small and
mainly case reports indicating possible publication bias.
Besides cardiovascular complications, other birth-related complications
may affect women with Marfan syndrome. However, an overall description
of such pregnancy-related complications still is not clear. Moreover,
most studies are from tertiary centres including only diagnosed Marfan
syndrome women but no controls. A prominent problem related to Marfan
syndrome care is the frequent occurrence of late diagnosis, sometimes
during pregnancy, or outright non-diagnosis, which complicates the
precise description of obstetric complications.
We hypothesized that morbidity in pregnancy is significantly increased
in women with Marfan syndrome, particularly due to cardiac
complications, to uterine, cervical and vaginal complications, as well
as due to preeclampsia and pre-term birth. Thus, our purpose was to
estimate pregnancy outcome, the overall morbidity as well as the risk of
aortic surgery and aortic dissection in relation to pregnancy in a
nationwide MFS cohort, where we included diagnosed as well as
pre-pregnancy in undiagnosed women with Marfan syndrome compared to age
matched controls.