Pregnancy, in vitro fertilization and cardiovascular outcomes in women with hereditary thoracic aortic diseases compared to controls: a retrospective register-based matched case-control study

Background Hereditary thoracic aortic diseases (HTAD) like Marfan syndrome (MFS), Loeys-Dietz syndrome (LDS), and vascular Ehler-Danlos syndrome (vEDS) combined with the hemodynamic and hormonal changes of pregnancy are associated with an increased risk of obstetric and cardiovascular complications. Purpose The aim of this study was to evaluate obstetric and cardiovascular outcomes during pregnancy and within 1 year postpartum in a national cohort of women with HTAD compared to matched controls. Methods We studied 99 women with HTAD, the majority of whom had MFS (n=89), LDS (n=5), and vEDS (n=5) in TheNational Registry of Congenital Heart Disease compared to 445 matched controls from National Statistics, using the Medical Birth Register, the National register of assisted reproduction, the National Patient Register and the Cause of Death register. Results Among the 170 pregnancies in women with HTAD, 151 occurred in women with MFS, 9 in women with LDS, and 10 in women with vEDS (Figure 1). Pregnant women with HTAD were younger, had a lower BMI, a lower frequency of in vitro fertilization (IVF), smoked less often, and had a lower rate of deliveries at term compared with controls (Table 1). HTAD was associated with a higher risk of preterm delivery, OR 2.1 (95% Cl: 1.2-3.6). Within 1 year after a pregnancy, a higher incidence of MACE was observed in women with MFS (n=4; 2.4%) compared with none in the controls (P=0.004). MACE consisted of hospitalization due to heart failure with aortic insufficiency (n=1, 0.6%) and non-ruptured aortic dissections (n=3, 2.0%). The patients with aortic dissection underwent aortic surgery: two within 10 days postpartum and one within 6 months after delivery. No women died during or within 1 year after pregnancy. Conclusion Women with HTAD seem to tolerate pregnancy well in regards of obstetric outcomes, except for an increased risk of preterm delivery. However, aortic dissection and heart failure may occur during and after pregnancy in women with MFS. Somewhat unexpectedly, IVF was performed only rarely among women with HTAD. This may partly reflect historical data, as approximately half of the pregnancies in women with HTAD were conceived before pre-implantation genetic testing (PGT) and IVF became more widely implemented in clinical practice. Nevertheless, it should be emphasized that when HTAD is genetically confirmed, preimplantation genetic testing and IVF ought to be considered. Pregnancy in patients with HTAD should be managed by a multidisciplinary team, and the importance of thorough pre-pregnancy counselling must not be overlooked.