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.