Author + information
- Iris M. van Hagen, MD,
- Denise van der Linde, MD, MSc, PhD,
- Ingrid M.B.H. van de Laar, MD, PhD,
- Laura Muiño Mosquera, MD,
- Julie De Backer, MD, PhD and
- Jolien W. Roos-Hesselink, MD, PhD∗ ()
- ↵∗Department of Cardiology, Erasmus University Medical Center, Thoraxcenter, Ba583a, P.O. Box 2040, 3000 CA Rotterdam, the Netherlands
Women with genetic aortic disease, such as Marfan syndrome, are at increased risk of pregnancy complications, in particular those with aortic dissection (1). Aneurysms-osteoarthritis syndrome (AOS) is an autosomal-dominant syndrome caused by SMAD3 mutations, and is characterized by arterial aneurysms and tortuosity in combination with osteoarthritis. There is a lack of data about the cardiovascular risks of pregnancy in women with SMAD3 mutation. Therefore, we collected data on the pregnancies of patients with SMAD3 mutation followed in our centers.
We included all women with a SMAD3 mutation who were previously enrolled in a prospective cohort study (2). Data regarding pregnancy were collected retrospectively, both through the medical file and by interview. In 2 patients with recent pregnancies, aortic dimensions measured with echocardiography or computed tomography before, during, and after pregnancy were available.
Seventeen women with SMAD3 mutation had 34 pregnancies. In all women except 2, the diagnosis of SMAD3 was made after pregnancy. At the time of diagnosis, osteoarthritis and orthopedic lesions were present in all but 1 patient, and vascular anomalies were present in at least 12 of 17 patients. Mean age at first conception was 26.0 ± 3.6 years (range 22 years to 33 years). There were 6 miscarriages in 4 women (23.6%). Twenty-eight pregnancies ended in live births, including 2 twins. No maternal mortality and no aortic dissection occurred. One patient developed pregnancy-induced hypertension and pre-eclampsia, and another patient reported gestational diabetes. Hydronephrosis occurred in 1 other patient. At least 4 patients were reported to have experienced severe pregnancy related pain in the pelvic area (24%). One patient had intrauterine growth restriction, resulting in an infant small-for-gestational age.
Three caesarean sections (CSs) were performed. One woman delivered by secondary CS due to failure to progress, and 2 women had a planned CS: 1 was performed for breech position, and the other was planned at 35 weeks because of increasing aortic diameters (Patient #2, Figure 1). No uterine rupture was reported. One neonate had lower urinary tract obstruction, and another infant was reported to have a cleft palate. No postpartum hemorrhage or other complications were reported.
No major cardiovascular complications occurred postpartum. Imaging before and after pregnancy is shown in Figure 1.
Pregnancy not only induces hemodynamic changes, with a 30% to 50% increase of cardiac output and 10% increase in heart rate, it may also influence the integrity of the aortic wall. This is suggested to be due to hormonal changes that affect, in particular, the matrix profile resulting in decreased artery stiffness (3). As AOS due to SMAD3 mutations is an aggressive aortic syndrome, concern exists around pregnancy in these patients. The current study describes 34 pregnancies in 17 women. No clear increased risk of aortic dissection or obstetric complications in these women was found. Conclusions of our results are limited by the retrospective nature of this study, with a risk of survivor bias, and the limited amount of patients included. Therefore, large prospective studies are warranted. In 2 patients with multiple aortic measurements, we observed no clear changes in Patient #1, whereas in Patient #2, the dimensions at the level of the sinus of Valsalva showed a tendency to increase. Future research must focus on aortic growth to further determine whether pregnancy has an effect on aortic diameters and poses women to an increased risk of aortic dissection. Finally, uterine rupture was not observed, but a number of patients spontaneously reported severe pain in the pelvic area, suggesting a link with pelvic joint pain.
This report, in combination with existing evidence on aortic syndromes caused by mutations in genes involved in the transforming growth factor–beta pathway such as Loeys-Dietz, can provide guidance for preconception counseling and management of pregnancy in patients with SMAD3 mutation. The guidelines on pregnancy and cardiovascular disease advise preconception surgery in women with SMAD3 mutation, when the aorta is ≥45 mm (4). Further management during pregnancy includes strict blood pressure control. CS in women with an aortic diameter >45 mm and vaginal delivery with epidural anesthesia when the aorta is <40 mm is advised. Between 40 mm and 45 mm, both strategies could be considered. We believe that these recommendations can be adapted to women with SMAD3 mutation. In our series, only 1 woman had a CS because of a dilated aorta. In the patients with vaginal delivery, no aortic complications occurred.
In conclusion, in the absence of prospective studies, our retrospective study shows no adverse outcome for pregnancy in women with SMAD3 mutation. However, counseling about the potential increased risk of pregnancy-related aortic complications remains warranted. In addition, pelvic joint pain might occur more often in these patients.
Please note: The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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