What are the management recommendations for pregnant women with alpha thalassemia?

Management of Alpha Thalassemia in Pregnancy

Critical Pre-Pregnancy Assessment

Women with alpha thalassemia considering pregnancy require comprehensive cardiac evaluation before conception, including cardiac MRI (T2) to assess iron loading, echocardiography for chamber dimensions and function, and electrocardiography.* 1, 2, 3

Cardiac Risk Stratification

• Cardiac T2 assessment is essential* as iron overload may result in cardiac complications during pregnancy's hemodynamic changes 1, 2
• Heart disease accounts for approximately 70% of deaths in transfusion-dependent thalassemia patients, making cardiac evaluation the highest priority 2
• Annual electrocardiography and echocardiography should already be part of routine care, but intensify monitoring if abnormalities detected 1, 3

Iron Overload Management

• Assess liver and cardiac iron burden before conception using MRI T2* imaging 1, 2
• Women with severe heart or liver iron overload should receive intensified chelation therapy before attempting pregnancy 1, 3
• Iron chelation must be discontinued during pregnancy due to teratogenic concerns, except deferoxamine may be restarted in the second/third trimester if severe iron overload threatens maternal cardiac function 1

Pregnancy Management by Trimester

First Trimester

• Discontinue all iron chelation therapy immediately due to teratogenic risk 1
• Maintain hemoglobin at approximately 10 g/dL through transfusion therapy 1
• Monitor for cardiac decompensation as blood volume begins expanding 1, 4

Second and Third Trimesters

• Maintain hemoglobin target of ~10 g/dL to ensure optimal fetal growth while minimizing transfusion burden 1
• Blood consumption typically increases during pregnancy, potentially worsening iron overload 1, 2
• Consider restarting deferoxamine chelation toward the end of second trimester in patients with severe cardiac or hepatic iron overload 1
• Monitor cardiac function carefully as increased blood volume and blood pressure changes may compromise heart function 1, 3

Thromboprophylaxis

Prophylaxis with heparin or low-molecular-weight heparin is mandatory, particularly in splenectomized patients and those with hemoglobin H disease. 1, 3

• Splenectomized thalassemia patients have particularly high thrombotic risk requiring careful anticoagulation monitoring 3
• Continue anticoagulation throughout pregnancy if significant iron overload or prior splenectomy 3

Monitoring During Pregnancy

Cardiac Surveillance

• Cardiac complications occur in 1.1% to 15.6% of pregnancies in women with thalassemia 1, 2
• Perform echocardiography each trimester to detect early cardiac decompensation 1
• Monitor for arrhythmias, particularly atrial fibrillation which occurs in up to 14% of patients with severe iron overload 2

Obstetric Complications

• Screen aggressively for gestational diabetes, preeclampsia, and hypertension as these occur frequently in thalassemia pregnancies 1, 2
• Spontaneous miscarriage and fetal loss occur in 9% to 33.3% of thalassemia pregnancies 1, 2
• Preterm birth rates are increased due to maternal and obstetric complications 1, 4

Fetal Monitoring

• Prenatal diagnosis should be offered to exclude fetal homozygous alpha thalassemia (hydrops fetalis) 4, 5
• Serial ultrasounds to monitor fetal growth given increased risk of intrauterine growth restriction 4
• Alpha thalassemia major (hydrops fetalis) requires specialized counseling about intrauterine transfusion options or pregnancy termination 5

Delivery Planning

Mode of Delivery

• Cesarean delivery rates range from 24% to 100% due to fetopelvic disproportion, osteoporosis, or maternal complications 1
• Consider assisted vaginal delivery or elective cesarean to avoid prolonged second stage and excessive Valsalva in patients with cardiac compromise 1
• Plan delivery at 38 weeks if maternal or fetal complications develop 6

Delivery Location

• Pregnancies must be managed at expert centers with multidisciplinary teams including hematology, maternal-fetal medicine, and cardiology 1, 4
• Availability of cardiac monitoring and intensive care support is essential 1

Postpartum Management

• Resume iron chelation therapy immediately postpartum if breastfeeding is not planned, or after weaning 1
• Continue thromboprophylaxis for at least 6 weeks postpartum 3
• Monitor for postpartum hemorrhage given underlying anemia 4
• Cardiac complications can occur postpartum; maintain surveillance 1, 2

Special Considerations by Alpha Thalassemia Type

Silent Carrier and Trait

• Generally well-tolerated in pregnancy with minimal complications 7
• Maintain awareness of mild anemia; avoid unnecessary iron supplementation 7, 8

Hemoglobin H Disease

• Requires transfusion support similar to beta thalassemia intermedia 7
• Higher risk of obstetric complications than trait carriers 4, 7
• Thromboprophylaxis is essential, especially if splenectomized 1, 3

Alpha Thalassemia Major (Hydrops Fetalis)

• Historically incompatible with life; now manageable with intrauterine transfusions 5
• At-risk families require pre-conceptual genetic counseling and options for preimplantation genetic testing 5
• Prenatal diagnosis mandatory with counseling about termination versus intrauterine transfusion therapy 5

Common Pitfalls to Avoid

• Never continue deferiprone or deferasirox during pregnancy - highly teratogenic 1
• Do not assume normal cardiac function based on clinical examination alone; imaging is mandatory 1, 2
• Avoid aggressive inotropic therapy if cardiac decompensation occurs, as this can be detrimental in thalassemia patients 3
• Do not overlook thromboprophylaxis in splenectomized patients - thrombotic risk is substantially elevated 1, 3
• Avoid multiple pregnancies through assisted reproduction; single embryo transfer strongly recommended to minimize cardiovascular stress 3