in the second stage of labor—may further facilitate right-to-left shunting, leading to a potential spiral of hypoxemic pulmonary vasoconstriction, hypotension, and death Overall, the high mortality of pregnancy in Eisenmenger syndrome has remained in the range of 30%.52 Outcomes may be better with early diagnosis and comprehensive management Targeted advanced pulmonary vascular therapies applied in specialized centers are likely to provide better outcomes, although reports of such improved outcomes are limited and the risk remains high.53,54 As a consequence, the widely held consensus is to advise against pregnancy in women with significant pulmonary hypertension of any cause and, in the event of unexpected pregnancy, to offer termination as the safest option Marfan Syndrome and Other Aortopathies Pregnancy-related hemodynamic and hormonal changes affect the structure of the aortic wall and increase the risk of dilation and dissection This phenomenon manifests as an increased risk of spontaneous dissection even in women with no known or diagnosable aortopathy Dissection risk is very low in otherwise normal women Dissection has best been described in women with Marfan syndrome, but those with other aortopathies that have genetic and/or pathologic similarities—such as familial thoracic aortic aneurysm and dissection syndromes, Loeys-Dietz syndrome, the aortopathy associated with bicuspid aortic valve, Turner syndrome, and vascular Ehlers-Danlos syndrome—are also at increased risk of aortic complications.55 In a prospective study of women with Marfan syndrome followed through 45 pregnancies, no significant change was found in the size of the aortic root in those initially exhibiting roots of normal size, but one-third of women with dilated roots or those having had prior aortic surgery experienced either aortic dissection or progressive aortic dilation.56 In a single-center study, favorable outcomes were reported in a large cohort of women carefully followed throughout pregnancy, although aortic growth rate increased during pregnancy and did not return to baseline after pregnancy.57 Although there are no trials demonstrating specific benefit during pregnancy of β-adrenergic–blocking drugs in women with aortopathy, many experts recommend such treatment during and after pregnancy in women with Marfan syndrome and other high-risk aortopathies in the hope that this may attenuate the risk of aortic dilation or dissection Prosthetic Heart Valves Women with any type of artificial heart valve are at increased risk for complications during pregnancy Bioprosthetic and mechanical valves each have advantages and disadvantages Careful consideration of the risks and benefits of each is required prior to selection of the type of prosthetic valve in a woman of childbearing age During pregnancy, normally functioning bioprosthetic valves are safer than mechanical valves because they are less thrombogenic and do not require ongoing anticoagulation Bioprosthetic valves, nonetheless, have limited durability, and women with these valves will generally require repeated surgery in the future Although some studies have suggested that pregnancy accelerates the degeneration of bioprosthetic valves, others have not supported this finding.58–60 Less information is available on the safety of homografts during pregnancy, although one study found no valve-related complications during pregnancy.61,62 Mechanical valves have better durability than bioprosthetic ones but are associated with significantly greater maternal and fetal risks during pregnancy Because pregnancy is a hypercoagulable state and anticoagulation can be difficult to manage with changing body weight during pregnancy, there is an increased risk of maternal thromboembolic events, of which approximately half are valvar thrombosis Many factors influence the risk of valve thrombosis and poor outcomes in pregnancy Valves in the mitral position carry higher thrombotic risks than those in the aortic position, as do early models of mechanical valves, such as those with balls in cages or the first generation of those with tilting discs However, one of the most important determinants of thrombosis risk is the type of anticoagulation used during pregnancy, as discussed later Anticoagulant therapy is complicated by risk of bleeding Systematic reviews have reported on maternal and fetal risks in pregnant women with mechanical valves.63,64 Risks of maternal and fetal adverse outcomes in pregnant women with mechanical valves according to type of anticoagulant used in pregnancy are shown in Table 80.3.63 Table 80.3 Maternal and Fetal Adverse Outcomes in Pregnant Women With Mechanical Valves Maternal Livebirth Anticoagulant-Related Anticoagulation Regimen Vitamin K antagonists (INR target 2.5–3.5) Sequential treatment LMWH alone UFH alone Mortality Estimate, % (95% CI) 0.9 (0.1–1.6) 2.7 (1.4–4.0) 2.0 (0.8–3.1) 5.8 (3.8–7.7) 2.9 (0.2–5.7) 8.7 (3.9–13.4) 3.4 (0–7.7) 11.2 (2.8–19.6) Thromboembolism Estimate, % (95% CI) Rate Estimate, % (95% CI) 64.5 (48.8– 80.2) 79.9 (74.3– 85.6) 92.0 (86.1– 98.0) 69.5 (37.8– 100) Fetal/Neonatal Adverse Events Estimate, % (95% CI) 2.0 (0.3–3.7)a 1.4 (0.3–2.5)a NA 7.6 (0.1–15.0)b a0.8% represent embryopathy and 2.1% represent fetopathy bAll cases represent fetopathy Estimates are presented as proportions per 100 affected pregnancies with 95% confidence intervals (CI) INR, International Normalized Ratio; LMWH, low-molecular-weight heparin; NA, not applicable; UFH, unfractionated heparin From D'Souza R, Ostro J, Shah PS, et al Anticoagulation for pregnant women with mechanical heart valves: a systematic review and meta-analysis Eur Heart J 2017;38:1509–1516 Options for anticoagulation include unfractionated heparin, low-molecularweight heparin, and oral anticoagulants such as warfarin and adjunctive aspirin Heparin does not cross the placenta and therefore is a safer alternative for the fetus Heparin given subcutaneously is difficult to manage, and is a less effective anticoagulant, with higher maternal thrombosis rates than warfarin Valvar thrombosis, which can be fatal, is less common in pregnancy when oral anticoagulants are used throughout compared with oral anticoagulants with unfractionated heparin substituted between 6 and 12 weeks of gestation or heparin throughout pregnancy Heparin may also cause maternal thrombocytopenia and osteoporosis Warfarin crosses the placenta and is associated with warfarin embryopathy in first-trimester use and with fetal intracranial bleeding, which is a risk throughout pregnancy The risk of warfarin embryopathy has been shown to be less if heparin is substituted from 6 until 12 weeks of gestation and also in women whose therapeutic dose of warfarin is less than 5 mg/day.65 Because intracranial bleeding can occur during vaginal delivery in a fetus exposed to maternal warfarin, heparin should be substituted at least 2 weeks prior to delivery or the fetus must be delivered by cesarean section Lowmolecular-weight heparin (LMWH) is easier to use than unfractionated heparin and has better bioavailability, but it is also associated with higher rates of