Acute aortic dissection related to pregnancy is rare, however represented the third most common cause of pregnancy-related cardiovascular death in the 2017 UK-MBBRACE report. The majority of women with pregnancy-related aortic dissection have an underlying inherited syndromic aortopathy, though this is often not recognised until an event. Data regarding the immediate and long-term effects of pregnancy on aortic outcome are not uniform due to publication and ascertainment biases, small sample sizes, inclusion of women whose dissection was the first presentation of the underlying disease, and incompleteness of collected data. Management recommendations are based on relatively low levels of evidence, and there is some variation between society guideline recommendations. This article seeks to review the available evidence regarding pregnancy-related aortic dissection in women inherited syndromic aortopathies, highlighting the importance of pre-conception counselling, genetic testing and a multi-disciplinary team approach to management.
BeyerSEDicksABShainkerSA, et al.Pregnancy-associated arterial dissections: a nationwide cohort study. Eur Heart J2020; 41: 4234–4242.
2.
JalnapurkarSSHGolandS, et al.Pregnancy associated aortic complications requiring surgery: a review of contemporary experience in 150 cases between 2000 to 2020. J Am Coll Cardiol2021: 3398.
3.
SLCSwanL. Aortopathy in pregnancy. Heart2022; 108: 1851–1857.
4.
RommensKLSandhuHKMillerCC, 3rd, et al.In-hospital outcomes and long-term survival of women of childbearing age with aortic dissection. J Vasc Surg2021; 74: 1135–1142. e1131.
5.
BravermanACMittauerEHarrisKM, et al.Clinical features and outcomes of pregnancy-related acute aortic dissection. JAMA Cardiol2021; 6: 58–66.
6.
De MartinoAMorgantiRFalcettaG, et al.Acute aortic dissection and pregnancy: review and meta-analysis of incidence, presentation, and pathologic substrates. J Card Surg2019; 34: 1591–1597.
7.
SawlaniNShroffAVidovichMI. Aortic dissection and mortality associated with pregnancy in the United States. J Am Coll Cardiol2015; 65: 1600–1601.
8.
EasterlingTRBenedettiTJSchmuckerBC, et al.Maternal hemodynamics and aortic diameter in normal and hypertensive pregnancies. Obstet Gynecol1991; 78: 1073–1077.
9.
FolkestadLHaldJDGramJ, et al.Cardiovascular disease in patients with osteogenesis imperfecta - a nationwide, register-based cohort study. Int J Cardiol2016; 225: 250–257.
10.
CeuppensASDe MeesterPVan De BruaeneA, et al.Aorta pathology and pregnancy-related risks in adult congenital cardiac disease: does the aorta dilate during pregnancy?Obstet Med2024; 17: 41–46.
11.
MurrayMLPepinMPetersonS, et al.Pregnancy-related deaths and complications in women with vascular Ehlers-Danlos syndrome. Genet Med2014; 16: 874–880.
12.
DuarteVERichardsonJNSinghMN. The impact of pregnancy in patients with thoracic aortic disease: epidemiology, risk assessment, and management considerations. Methodist Debakey Cardiovasc J2024; 20: 51–58.
13.
VanderJagtKButlerMG. Ehlers-Danlos syndrome and other heritable connective tissue disorders that impact pregnancies can be detected using next-generation DNA sequencing. Arch Gynecol Obstet2019; 300: 491–493.
14.
GesslerNWohlmuthPAnwarO, et al.Sleep apnea predicts cardiovascular death in patients with Marfan syndrome: a cohort study. EPMA J2022; 13: 451–460.
15.
KohlerMBlairERisbyP, et al.The prevalence of obstructive sleep apnoea and its association with aortic dilatation in Marfan's syndrome. Thorax2009; 64: 162–166.
16.
PhamTTDavisSMTongS, et al.High prevalence of obstructive sleep-disordered breathing in pediatric patients with turner syndrome. Otolaryngol Head Neck Surg2024; 170: 905–912.
17.
SedkyKGaislTBennettDS. Prevalence of obstructive sleep apnea in joint hypermobility syndrome: a systematic review and meta-analysis. J Clin Sleep Med2019; 15: 293–299.
18.
StoberlASGaislTGiuntaC, et al.Obstructive sleep apnoea in children and adolescents with Ehlers-Danlos syndrome. Respiration2019; 97: 284–291.
19.
GaislTGiuntaCBrattonDJ, et al.Obstructive sleep apnoea and quality of life in Ehlers-Danlos syndrome: a parallel cohort study. Thorax2017; 72: 729–735.
20.
GravholtCHAndersenNHChristin-MaitreS, et al.Clinical practice guidelines for the care of girls and women with Turner syndrome. Eur J Endocrinol2024; 190: G53–G151.
21.
VerbraeckenJDeclerckAVan de HeyningP, et al.Evaluation for sleep apnea in patients with Ehlers-Danlos syndrome and Marfan: a questionnaire study. Clin Genet2001; 60: 360–365.
22.
DominguezJECantrellSHabibAS, et al.Society of anesthesia and sleep medicine and the society for obstetric anesthesia and perinatology consensus guideline on the screening, diagnosis, and treatment of obstructive sleep apnea in pregnancy. Obstet Gynecol2023; 142: 403–423.
23.
LouisJMKochMAReddyUM, et al.Predictors of sleep-disordered breathing in pregnancy. Am J Obstet Gynecol2018; 218: 521 e521–521 e512.
24.
LebenthalYLevySSofrin-DruckerE, et al.The natural history of metabolic comorbidities in turner syndrome from childhood to early adulthood: comparison between 45,X monosomy and other karyotypes. Front Endocrinol (Lausanne)2018; 9: 27.
25.
GravholtCHAndersenNHConwayGS, et al.Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati international Turner syndrome meeting. Eur J Endocrinol2017; 177: G1–G70.
26.
CameronNABlylerCABelloNA. Oral contraceptive pills and hypertension: a review of current evidence and recommendations. Hypertension2023; 80: 924–935.
27.
ShankarRKBackeljauwPF. Current best practice in the management of Turner syndrome. Ther Adv Endocrinol Metab2018; 9: 33–40.
28.
BurtEDaviesMCYasminE, et al.Fertility and pregnancy outcomes in women with Turner syndrome: a single centre experience. Clin Endocrinol (Oxf)2024; 101: 51–59.
29.
GrewalJValenteAMEgbeAC, et al.Cardiovascular outcomes of pregnancy in turner syndrome. Heart2021; 107: 61–66.
30.
HynesJSKullerJAGoldsteinSA, et al.Increased risk of aortic dissection associated with pregnancy in women with Turner syndrome: a systematic review. Obstet Gynecol Surv2020; 75: 566–575.
31.
CadoretFParinaudJBettiolC, et al.Pregnancy outcome in Turner syndrome: a French multi-center study after the 2009 guidelines. Eur J Obstet Gynecol Reprod Biol2018; 229: 20–25.
32.
AndreHPimentelCVeauS, et al.Pregnancies and obstetrical prognosis after oocyte donation in Turner syndrome: a multicentric study. Eur J Obstet Gynecol Reprod Biol2019; 238: 73–77.
33.
HagmanALoftAWennerholmUB, et al.Obstetric and neonatal outcome after oocyte donation in 106 women with Turner syndrome: a Nordic cohort study. Hum Reprod2013; 28: 1598–1609.
34.
BernardVDonadilleBZenatyD, et al.Spontaneous fertility and pregnancy outcomes amongst 480 women with Turner syndrome. Hum Reprod2016; 31: 782–788.
35.
Alvaro MercadalBImbertRDemeestereI, et al.Pregnancy outcome after oocyte donation in patients with Turner's syndrome and partial X monosomy. Hum Reprod2011; 26: 2061–2068.
36.
van den BersselaarLMvan de LaarIBaarsMJH, et al.Pregnancy and delivery outcomes in vascular Ehlers-Danlos syndrome: a retrospective multicentre cohort study. BJOG2025 .
37.
UnderhillLABarbaritaCCollisS, et al.Association of maternal versus fetal Ehlers-Danlos syndrome status with poor pregnancy outcomes. Reprod Sci2022; 29: 3459–3464.
38.
FriseCJPitcherAMackillopL. Loeys-Dietz syndrome and pregnancy: the first ten years. Int J Cardiol2017; 226: 21–25.
39.
CauldwellMSteerPJCurtisS, et al.Maternal and fetal outcomes in pregnancies complicated by the inherited aortopathy Loeys-Dietz syndrome. BJOG2019; 126: 1025–1031.
40.
WhelanARThorsenMMMacCarrickG, et al.Cardiovascular and obstetrical outcomes among delivering patients with Marfan or Loeys-Dietz syndrome: a retrospective analysis by hospital delivery setting. Am J Obstet Gynecol MFM2024; 6: 101340.
41.
KunishigeHIshibashiYKawasakiM, et al.Surgical treatment for acute type A aortic dissection during pregnancy (16 weeks) with Loeys-Dietz syndrome. Gen Thorac Cardiovasc Surg2012; 60: 764–767.
42.
LoeysBLSchwarzeUHolmT, et al.Aneurysm syndromes caused by mutations in the TGF-beta receptor. N Engl J Med2006; 355: 788–798.
MeiPML. Cardiomyopathy in pregnancy complicated by Loeys-Dietz syndrome. Circulation2024; 150: A4143083.
45.
RussoMLSukhavasiNMathurV, et al.Obstetric management of Loeys-Dietz syndrome. Obstet Gynecol2018; 131: 1080–1084. 2018/05/10.
46.
ThomasKEHoganJPitcherA, et al.Loeys-Dietz syndrome in pregnancy. Obstet Med2021; 14: 42–45. 2021/05/18.
47.
IsselbacherEMPreventzaOHamilton BlackJ, 3rd, et al.ACC/AHA guideline for the diagnosis and management of aortic disease: a report of the American Heart Association/American College of Cardiology joint committee on clinical practice guidelines. Circulation 20222022; 146: e334–e482.
48.
RobertsEAPistnerAOsobamiroO, et al.Beta-blocker use during pregnancy correlates with less aortic root dilatation in patients with Marfan's syndrome. Aorta (Stamford)2023; 11: 63–70.
49.
RyuRJEyalSEasterlingTR, et al.Pharmacokinetics of metoprolol during pregnancy and lactation. J Clin Pharmacol2016; 56: 581–589.
50.
BaderkhanHWanhainenAStenborgA, et al.Celiprolol treatment in patients with vascular Ehlers-Danlos syndrome. Eur J Vasc Endovasc Surg2021; 61: 326–331.
51.
OngKTPerduJDe BackerJ, et al.Effect of celiprolol on prevention of cardiovascular events in vascular Ehlers-Danlos syndrome: a prospective randomised, open, blinded-endpoints trial. Lancet2010; 376: 1476–1484.
52.
LacroRVDietzHCSleeperLA, et al.Atenolol versus losartan in children and young adults with Marfan's syndrome. N Engl J Med2014; 371: 2061–2071.
53.
van AndelMMIndrakusumaRJalalzadehH, et al.Long-term clinical outcomes of losartan in patients with Marfan syndrome: follow-up of the multicentre randomized controlled COMPARE trial. Eur Heart J2020; 41: 4181–4187.
54.
ChiuHHWuMHWangJK, et al.Losartan added to beta-blockade therapy for aortic root dilation in Marfan syndrome: a randomized, open-label pilot study. Mayo Clin Proc2013; 88: 271–276.
55.
DoyleJJDoyleAJWilsonNK, et al.A deleterious gene-by-environment interaction imposed by calcium channel blockers in Marfan syndrome. Elife2015; 4.
56.
CauldwellMSteerPJAdamsonD, et al.Pregnancies in women with Turner syndrome: a retrospective multicentre UK study. BJOG2022; 129: 796–803.
57.
MakamHSiddiquiFPatwardhanA, et al.Peripartum considerations and challenges in the management of type IV Ehlers-Danlos syndrome. BMJ Case Rep2021; 14.
58.
MortonATeasdaleS. Review article: investigations and the pregnant woman in the emergency department - part 2: point-of-care ultrasound, electrocardiography, respiratory function tests and radiology. Emerg Med Australas2018; 30: 749–753.
59.
WhelanARRingelMEShalhubS, et al.Obstetric considerations for aortopathy in pregnancy. Ann Cardiothorac Surg2023; 12: 526–535.
60.
HamlynELDouglassCAPlaatF, et al.Low-dose sequential combined spinal-epidural: an anaesthetic technique for caesarean section in patients with significant cardiac disease. Int J Obstet Anesth2005; 14: 355–361.
61.
RoofthooftEJoshiGPRawalN, et al.PROSPECT Guideline for elective caesarean section: an update. Anaesthesia2023; 78: 1170–1171.
62.
KarthikeyanAVenkat-RamanN. Hypermobile Ehlers-Danlos syndrome and pregnancy. Obstet Med2018; 11: 104–109.
63.
CobergerEDJensenBPDalrympleJM. Transfer of candesartan into human breast milk. Obstet Gynecol2019; 134: 481–484.
64.
HabashiJPMacFarlaneEGBagirzadehR, et al.Oxytocin antagonism prevents pregnancy-associated aortic dissection in a mouse model of Marfan syndrome. Sci Transl Med2019: 11.
65.
BowenCJCalderon GiadrosicJFBurgerZ, et al.Targetable cellular signaling events mediate vascular pathology in vascular Ehlers-Danlos syndrome. J Clin Invest2020; 130: 686–698.
66.
MengXHanJWangL, et al.Aortic dissection during pregnancy and postpartum. J Card Surg2021; 36: 2510–2517.
67.
CoroyannakisCTomeMWatt-CooteI, et al.Pregnancy following personalised aortic root support in Marfan syndrome. Obstet Med2023; 16: 200–202.
68.
FrostCNRSmithITesarP. PEARS: an alternate procedure in pregnant patients with Marfan syndrome. Heart, Lung and Circulation2020; 29: S315.
