# Pregnancy-Related Vascular Outcomes in Loeys–Dietz Syndrome: A Retrospective Cohort Study and Case Series

**Authors:** Amal Youssef, Hend Bcharah, Hussein Abdul Nabi, George Bcharah, Luke Dreher, Mohammed Alaa Raslan, Fares Jamal, Linnea Baudhuin, Mayowa A. Osundiji, Yuxiang Wang, Christine Firth, Fadi Shamoun

PMC · DOI: 10.3390/medsci14010079 · Medical Sciences · 2026-02-11

## TL;DR

This study examines pregnancy and vascular outcomes in women with Loeys–Dietz syndrome and finds no major aortic complications during or after pregnancy.

## Contribution

The study provides new insights into pregnancy-related vascular risks and diagnostic timing in Loeys–Dietz syndrome patients.

## Key findings

- Pregnancy and postpartum periods in LDS patients did not result in acute aortic catastrophes.
- Women without prior pregnancy were diagnosed with LDS at a younger age.
- Vascular complications occurred in a significant proportion of pregnant LDS women but did not differ by pregnancy history.

## Abstract

Background: Loeys–Dietz syndrome (LDS) is an autosomal dominant aortopathy characterized by aggressive aneurysm formation and arterial dissections. Pregnancy-related outcomes and timing of LDS diagnosis remain poorly characterized. Methods: Demographics, genetic, obstetric, and vascular data was collected from genetically or clinically confirmed individuals with LDS seen at the three Mayo Clinic sites from 2018 to 2025. Aneurysm progression, new aneurysm formation, and arterial dissections were recorded across all vascular beds. Vascular events were assessed during pregnancy, within 12 months postpartum, and during breastfeeding. Comparative analyses were performed between women with and without a history of pregnancy, and a single-arm descriptive analysis was conducted among patients who experienced vascular complications during the peripartum period. Continuous variables were compared using the Mann–Whitney U test, while categorical variables were analyzed using chi-square or Fisher exact tests. Results: Of 47 women with LDS, 24 had a history of pregnancy, accounting for 54 pregnancies. In the comparative analysis, age at LDS diagnosis differed significantly between women with and without a prior pregnancy: women without prior pregnancy were diagnosed at a younger age (median 23.5 years [IQR 10.8–41.0], n = 23) than those who had been pregnant (median 53.5 years [IQR 43.0–59.3], n = 24). Among pregnant women, the median age at first pregnancy was 28 years (IQR 23–34); only 4 (16.7%) knew their diagnosis before pregnancy. Of 54 pregnancies, 40 (74.1%) resulted in live birth, with 23 (57.5%) vaginal and 17 (42.5%) cesarean deliveries; preterm delivery occurred in 1 (2.5%) pregnancy, and postpartum hemorrhage in 2 (5.0%). No maternal deaths, aortic dissections, or uterine ruptures occurred during gestation or the first postpartum year. In addition, 14 women (58.3%) developed aneurysms, 6 (25.0%) experienced at least one arterial dissection, and 7 (29.2%) required surgical repair, predominantly involving the ascending and abdominal aorta. The prevalence of vascular complications did not differ significantly between groups. Conclusions: In this LDS cohort, pregnancy and the early postpartum period were not accompanied by acute aortic catastrophes, despite frequent diagnostic delay. Although women without prior pregnancy were diagnosed at a younger age, the overall burden of vascular and morphologic complications did not differ significantly by pregnancy history. These findings highlight the importance of long-term cardiovascular follow-up in women with LDS.

## Linked entities

- **Diseases:** Loeys–Dietz syndrome (MONDO:0018954)

## Full-text entities

- **Genes:** TGFBR2 (transforming growth factor beta receptor 2) [NCBI Gene 7048] {aka AAT3, FAA3, LDS1B, LDS2, LDS2B, MFS2}, TGFB3 (transforming growth factor beta 3) [NCBI Gene 7043] {aka ARVD, ARVD1, LDS5, RNHF, TGF-beta3}, SMAD2 (SMAD family member 2) [NCBI Gene 4087] {aka CHTD8, JV18, JV18-1, LDS6, MADH2, MADR2}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, TGFB2 (transforming growth factor beta 2) [NCBI Gene 7042] {aka CAEND2, G-TSF, LDS4, TGF-beta2}, TGFBR1 (transforming growth factor beta receptor 1) [NCBI Gene 7046] {aka AAT5, ACVRLK4, ALK-5, ALK5, ESS1, LDS1}, SMAD3 (SMAD family member 3) [NCBI Gene 4088] {aka HSPC193, HsT17436, JV15-2, LDS1C, LDS3, MADH3}
- **Diseases:** FMD (MESH:D005352), aortic (MESH:D001018), aortic and arterial complications (MESH:D008107), Ehlers-Danlos syndrome (MESH:D004535), injury to (MESH:D014947), carotid, cerebral, splenic, and mesenteric aneurysms (MESH:D002532), scoliosis (MESH:D012600), sinus of Valsalva (MESH:D012852), deaths (MESH:D003643), autosomal dominant connective tissue disorder (MESH:D003240), aortic catastrophes (MESH:D002388), hypertension (MESH:D006973), uterine rupture (MESH:D014597), aortic dissection (MESH:D000784), Diabetes mellitus (MESH:D003920), atrial fibrillation (MESH:D001281), vascular disease (MESH:D014652), aortic wall structural weakness (MESH:D018908), valve (MESH:D006349), aneurysmal dilatation of the ophthalmic artery (MESH:D002311), Aneurysm (MESH:D000783), vasculopathy (MESH:D000090122), cardiogenic shock (MESH:D012770), preterm birth (MESH:D047928), myocardial infarction (MESH:D009203), blood loss (MESH:D016063), aortic aneurysms (MESH:D001014), DM (MESH:D009223), autosomal dominant aortopathy (MESH:C566739), deep vein thrombosis (MESH:D020246), ascending aortic aneurysm (MESH:D000094625), arterial dissection (MESH:D000094665), heart failure (MESH:D006333), miscarriage (MESH:D000022), LDS types 1 and 2 (OMIM:610168), aortic root enlargement (MESH:D000094628), LDS (MESH:D055947), systolic dysfunction (MESH:D006331), Marfan syndrome (MESH:D008382), SMA dissection (MESH:D014897), postpartum hemorrhage (MESH:D006473), aortic regurgitation (MESH:D001022), Vascular Complications (MESH:D003925), (superior mesenteric artery (SMA), hepatic, splenic), iliac, and cerebral aneurysms (MESH:D013478), osteoarthritis (MESH:D010003), vascular fragility (MESH:D005600), stenosis (MESH:D003251), bicuspid (MESH:D000082882), SCAD (MESH:C565153), abdominal aortic dissection (MESH:D000094631), DVT (OMIM:612862), pulmonary hypertension (MESH:D006976), arteriopathies (MESH:D020212), arterial tortuosity (MESH:C565942)
- **Chemicals:** BioRender (-), AC (MESH:D000186), ASA (MESH:D001241), progesterone (MESH:D011374)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** 844T>C, 455delC, 1G>C, 1176delinsCG, 1378C>T

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## References

19 references — full list in the complete paper: https://tomesphere.com/paper/PMC12921812/full.md

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Source: https://tomesphere.com/paper/PMC12921812