Marfan syndrome (MS) is the most common genetic disease associated with connective tissue defects.1–4 Aortic involvement (and aortic root involvement in particular) is the main prognostic factor, as it places patients at an increased risk of progressive dilation, rupture, or dissection. Aortic events are the main cause of mortality and reduced life expectancy in MS.5–7

The risk of aortic complications in MS increases during pregnancy due to hemodynamic and hormonal changes associated with increased cardiac output and estrogen/progesterone levels and consequently increased cardiovascular stress.8,9

Recent studies of pregnancy in MS have reported aortic dissection rates of 3% to 8%.10,11 In this setting, pregnant women have a 5- to 23-fold increased risk of dissection compared with nonpregnant women12,13 and a 20 000-fold increased risk compared with the general population.14 Size of the aortic diameter is the main risk factor, but even women with an aortic root diameter <40mm have a 1% risk of dissection.15,16

Current European guidelines recommend aortic surgery before pregnancy in women with an aortic diameter >45mm17 or 40mm to 45mm in the presence of risk factors (family history of early aortic dissection or rapid growth). The American College of Cardiology/American Heart Association guidelines, by contrast, recommend elective aortic surgery before pregnancy in women with an aortic diameter >40mm.18

The above indications, however, are based on clinical experience from case series, observational studies, and reviews.19–21 In addition, more than 50% of the women in these studies were diagnosed with MS during or after pregnancy and consequently did not benefit from the latest prevention and medical treatment recommendations.22,23

In this article, we present our multicenter experience with the management of MS in dedicated MS units and analyze the occurrence of aortic events during pregnancy and postpartum.

Observational, retrospective study of patients diagnosed with MS based on the Ghent criteria and genetic studies. We included patients managed at a dedicated MS unit at Hospital Universitario Puerta de Hierro in Madrid and Hospital Universitario Vall d’Hebron in Barcelona. These units offer full family screening and diagnostic services as well as multidisciplinary care involving periodic follow-up and current prevention and treatment measures (administration of beta-blockers or losartan, relative limitation of physical activity, periodic echocardiographic assessments and computed tomography (CT)/magnetic resonance (MR) angiography, and preventive surgery in patients with an aortic diameter ≥50mm (or ≥45mm if there are risk factors).24

The study was approved by the ethics committee at our hospital and all patients gave their written informed consent for the retrospective analysis of their data.

This is the first Spanish study and one of the largest series to date to analyze the risk of peripartum aortic events in women with MS followed up at dedicated units and managed according to the latest prevention and treatment recommendations.24

Little has been published on the risk of aortic events during pregnancy in MS, and most studies have focused on women who were not managed at a dedicated unit before becoming pregnant. Studies have also largely focused on the risk of aortic dissection,11,13,23,25 with little attention paid to other clinically relevant aortic events, such as aortic growth during pregnancy.

The overall rate of aortic events during pregnancy in our series of MS patients was 3.7% (2 type A dissections, 1 type B dissection, and 2 cases of rapid aortic growth). The specific dissection rate was 2.2%, which is lower than most rates reported in previous studies (1.9%-7.9%).11–13,23,25 This lower rate might be due to close monitoring at dedicated MS units and a higher rate of beta-blocker use before and during pregnancy (82%). In a multicenter study of 151 pregnant women with MS in the United Kingdom, Cauldwell et al.25 reported that 64.2% of women had been treated with beta-blockers and 1.9% experienced aortic dissection. By contrast, Lind et al.26 reported 5 dissections in 44 women with 147 pregnancies treated with beta-blockers. In the GenTAC (Genetically Triggered Aortic Aneurysms and Cardiovascular Conditions) registry, 4.4% of pregnant women with MS experienced an aortic event and fewer than 50% were treated with peripartum beta-blockers.13

Mean aortic diameter growth during pregnancy was 0.7mm in our series, with faster growth observed in the third trimester and postpartum period. Renard et al.27 also found that aortic diameters grew fastest in the postpartum period and then stabilized. These findings highlight the importance of continued surveillance of women with MS during the peripartum period.

The low rate of aortic events in our series of MS patients prevented us from identifying risk factors for complications during pregnancy. We only observed a tendency towards an increased risk in women with a prepregnancy aortic diameter > 40mm: 18.7% of these women experienced an aortic event vs just 2.7% of those with a diameter <40mm (odds ratio=3.32; P=.058).

The 5 cases of aortic dissection reported in the UK multicenter study occurred in women with an aortic diameter <45mm.25 In a retrospective review of 852 women with MS (1112 pregnancies), Kim et al.11 reported 88 aortic dissections, and 63% of the women had an aortic diameter ≥40mm.

The above findings are consistent with the US guideline recommendation to perform preventive aortic surgery in women with MS with a prepregnancy aortic diameter >40mm.18 The European Guidelines, by contrast, establish a threshold of 45mm.17

Of note, even women who do not have a dilated aortic root before they become pregnant, or who undergo preventive aortic root surgery, have an increased risk of dissection during pregnancy. Cauldwell et al.25 reported a rate of 3.4% for type B aortic dissections in pregnant women with MS who had undergone preventive aortic root surgery. Prepregnancy MR/CT angiography should be performed in all women with MS.

Delivery route is not a risk factor for aortic events. In our series, 62% of the deliveries were vaginal, supporting previous reports of the safety of vaginal delivery in women with MS.11,23,25,28 Cesarean section should be performed when deemed necessary by the treating obstetrician and in patients with a history of aortic events or an aortic diameter ≥40mm.

In line with previous studies, all the aortic events in our series occurred in the third trimester or postpartum. This is consistent with the physiology of pregnancy, where cardiovascular demands peak at 32 weeks and remain high for the first 3 months postpartum.8,29 Habashi et al.30 showed a possible association between risk of aortic events and oxytocin levels, which increase in the last few months of pregnancy and remain high during breastfeeding. Again, these findings highlight the importance of follow-up and close monitoring of pregnant women with MS, especially in the third trimester and postpartum.

Pregnancy is associated with an increased risk of aortic events in women with MS, particularly in the third trimester and postpartum period. The option of preventive surgery for women with an aortic diameter ≥40mm should be evaluated in hospitals with experience in this field. It is important to provide an early diagnosis, prepregnancy assessment of the entire aorta, beta-blocker administration, and close monitoring during pregnancy, especially during the last trimester and postpartum period.

No funding of any nature was received for the preparation of this manuscript.

C.E. Martín: conceptualization, data collection, design, analysis, and original draft preparation. A. Evangelista and G. Teixidó: data collection and review of manuscript content. S. Villar, S. Serrano-Fiz, V. Ospina, S. Mingo, V. Moñivas, D. Martínez, and J. Villarreal: review of intellectual content. A. Forteza: conceptualization, interpretation, and review of intellectual content.

There are no conflicts of interest.