How to manage a pregnant patient with a neurodevelopmental tumor (NTDT) and pulmonary hypertension?

Management of Non-Transfusion Dependent Thalassemia (NTDT) in Pregnancy with Pulmonary Hypertension

Critical Initial Action

Pregnancy in the setting of pulmonary hypertension should be avoided, and when it does occur, immediate referral to a specialized pulmonary hypertension center with multidisciplinary expertise (including pulmonary hypertension specialists, high-risk obstetrics, and cardiovascular anesthesiology) is mandatory, as maternal mortality remains 12-33% even with modern management. 1, 2

Immediate Assessment and Risk Stratification

• Confirm pulmonary hypertension severity through comprehensive echocardiographic assessment, with MRI without gadolinium if echocardiography is insufficient 2
• Assess functional status using WHO functional class, as this impacts treatment intensity 1
• Early hospitalization is crucial once the fetus is viable for closer hemodynamic monitoring 1, 2
• Maternal mortality risk is highest in the last trimester and first months postpartum due to pulmonary hypertensive crises, pulmonary thrombosis, or refractory right heart failure 2

Pregnancy Counseling and Termination Discussion

• Offer pregnancy termination, especially in early pregnancy, as this remains the safest option given 12-33% maternal mortality risk 1, 2
• If the patient refuses termination (as in your case), document informed consent regarding the substantial risks to both mother and fetus 1
• Neonatal survival rates are 87-89%, but there is increased risk of small-for-gestational-age infants and congenital anomalies 1

Hemodynamic Support and Monitoring

• Institute invasive hemodynamic monitoring with pulmonary artery catheter for close monitoring and titration of therapy 1
• Maintain circulating volume carefully with cautious fluid management, as both volume overload and depletion are dangerous 1, 2
• Provide supplemental oxygen to maintain saturations >91% if hypoxemia is present 1, 2
• Avoid systemic hypotension, hypoxia, and acidosis at all costs, as these precipitate right heart failure 2

Pulmonary Vasodilator Therapy

First-Line Agents (Pregnancy-Compatible)

• Initiate or continue intravenous epoprostenol (pregnancy category B), starting at 2-4 ng/kg/min several weeks before delivery if not already on therapy 3, 4, 5

  • Animal studies at 2.5-4.8 times the maximum recommended human dose showed no fetal harm 3
  • This is the most extensively studied agent in pregnancy with PAH 5

• Consider inhaled iloprost (pregnancy category C) as an alternative or adjunct, typically administered every 2-4 hours 4, 5

  • Successfully used in case reports without congenital abnormalities 4, 5

• Add oral sildenafil (pregnancy category B) for additional pulmonary vasodilation 4, 5

  • Case reports demonstrate successful outcomes when combined with prostacyclin therapy 4, 5

Agents to AVOID

• Do NOT use endothelin receptor antagonists (bosentan, ambrisentan, macitentan) - these are pregnancy category X with evidence of serious fetal abnormalities 1
• Do NOT use riociguat - pregnancy category X 1
• Avoid estrogen-containing contraceptives postpartum due to VTE risk 1

Anticoagulation Strategy

• Administer full-dose low-molecular-weight heparin instead of warfarin for thromboprophylaxis throughout pregnancy 2, 5
• Consider anticoagulation particularly if there are signs of heart failure or established indication outside pregnancy 2

Supportive Therapy

• Diuretics (furosemide) for pulmonary congestion, but use cautiously as they may decrease placental blood flow 1
• Dobutamine if inotropic support is needed 1
• Digoxin may be used but monitor levels closely, as epoprostenol decreases digoxin clearance by 15% 3

Delivery Planning

Timing

• Plan delivery at 32-34 weeks if maternal condition deteriorates, balancing fetal maturity against maternal risk 4, 6
• Administer corticosteroids for fetal lung maturity if delivery anticipated before 34 weeks 1

Mode of Delivery

• Cesarean section is preferred for patients with severe symptoms or Eisenmenger syndrome 2
• Vaginal delivery with epidural analgesia and elective instrumental delivery may be considered for stable patients 2
• The optimal mode remains controversial, but avoid general anesthesia due to increased mortality risk 1, 2

Anesthetic Considerations

• Epidural analgesia is preferred over general anesthesia 2
• Maintain heart rate carefully, as cardiac output is heart-rate dependent; have anticholinergic agents readily available 1
• Avoid bradycardia and systemic vasodilation that can precipitate cardiovascular collapse 1

Critical Postpartum Period (Highest Risk)

• Maintain intensive monitoring for at least 72 hours postpartum, as this is when most maternal deaths occur 2, 7
• Dramatic volume shifts occur immediately postpartum with decompression of vena cava and return of uterine blood to systemic circulation 1
• Continue pulmonary vasodilator therapy and oxygen supplementation 4
• Monitor for pulmonary hypertensive crises and right heart failure with aggressive intervention if deterioration occurs 2

Common Pitfalls to Avoid

• Delayed referral to specialized centers - transfer immediately upon diagnosis 2, 7
• Underestimating moderate pulmonary hypertension - even moderate forms worsen significantly during pregnancy 2
• Inadequate postpartum monitoring - most deaths occur in the immediate postpartum period 2, 7
• Fluid overload during delivery - maintain meticulous fluid balance 1
• Using teratogenic pulmonary vasodilators - avoid all endothelin receptor antagonists and riociguat 1

Long-Term Considerations

• Pulmonary hypertension may progress during pregnancy and remain worse postpartum, even with successful delivery 1
• Dual mechanical barrier contraception is mandatory postpartum to prevent future pregnancies 1
• Maternal mortality in this population remains 16.7% even with optimal management 6