Alpha thalassemia (AT) is an inherited blood disorder that reduces the body’s ability to produce alpha-globin chains, a component of hemoglobin. Hemoglobin is the protein responsible for carrying oxygen from the lungs to all tissues. Impaired alpha-globin production reduces oxygen-carrying capacity, leading to anemia. This condition is a concern during pregnancy because the shared maternal-fetal circulation can be severely compromised in the most serious forms. Severity depends directly on the number of affected genes, dictating the risk to the developing fetus and the pregnant person.
Genetic Inheritance and Carrier Screening
Alpha thalassemia is inherited through four alpha-globin genes, with two genes located on each chromosome copy. Individuals can inherit a deletion or inactivation in one, two, three, or all four genes. Carrier status applies when an individual has one or two affected genes but does not display severe symptoms.
Carrier screening is performed before conception or early in pregnancy, particularly for people from high-risk ancestry groups, such as Southeast Asia, Africa, the Mediterranean, or the Middle East. Initial screening involves a Complete Blood Count (CBC) to check for low Mean Corpuscular Volume (MCV) or Mean Corpuscular Hemoglobin (MCH). These results indicate smaller-than-normal red blood cells, a common sign of a thalassemia trait.
If screening suggests a carrier state, the partner is tested to determine the risk of having a child with a severe form of the disorder. If both partners are carriers, genetic counseling reviews the specific risk percentage based on their genetic variations. Further testing, such as Hemoglobin (Hb) analysis or DNA sequencing, is then used to accurately define the carrier status and the potential risk to the fetus.
Varying Severity Levels and Fetal Outcomes
Alpha thalassemia is categorized by the number of non-functional alpha-globin genes, ranging from one to four. Silent Carrier status (one gene missing) results in no clinical symptoms and is usually only detectable through genetic testing. The Alpha Thalassemia Trait (two genes deleted) leads to mild or no anemia. A pregnancy where the fetus has the trait is generally not associated with adverse outcomes.
The deletion of three alpha-globin genes results in Hemoglobin H (HbH) disease, causing chronic, moderate to severe anemia, an enlarged spleen and liver, and sometimes jaundice. Fetuses with HbH disease may experience a higher risk of complications, including lower Apgar scores, and require lifelong medical management.
The most severe form, resulting from the deletion of all four alpha-globin genes, is Hemoglobin Bart’s (Hb Bart’s) Hydrops Fetalis. In this condition, the fetus cannot produce functional hemoglobin, leading to severe anemia and heart failure. This causes hydrops fetalis, a dangerous fluid buildup in the body cavities and tissues. This diagnosis was historically associated with stillbirth or death shortly after birth. A pregnancy affected by Hb Bart’s also carries serious risks for the mother, including preeclampsia, premature delivery, and maternal mirror syndrome.
Diagnostic Testing and Fetal Surveillance
Once carrier screening identifies a couple at high risk, detailed fetal surveillance is initiated. Non-invasive monitoring involves serial ultrasounds to assess for signs of fetal anemia and heart strain, such as hydrops fetalis or an increase in fetal heart size. These signs often become visible in the second and third trimesters.
To definitively confirm the fetal genotype, invasive diagnostic procedures are offered. Chorionic Villus Sampling (CVS) can be performed between 11 and 14 weeks, or Amniocentesis can be conducted after 15 weeks. Both procedures collect fetal cells for DNA analysis to identify the exact number of gene deletions. If a severe diagnosis is suspected or confirmed, Percutaneous Umbilical Cord Blood Sampling (PUBS) may be performed to directly measure the fetal hemoglobin level.
Pregnancy Management and Delivery Planning
Management for a pregnancy confirmed to be affected by severe alpha thalassemia requires a coordinated, multidisciplinary team approach. The team includes maternal-fetal medicine specialists, pediatric hematologists, and neonatologists. For fetuses diagnosed with Hb Bart’s Hydrops Fetalis, the primary in-utero treatment option is Intrauterine Blood Transfusion (IUT).
IUTs, often beginning around 18 to 25 weeks, involve transfusing healthy red blood cells directly into the fetal umbilical vein under ultrasound guidance. These transfusions aim to reverse anemia and hydrops, improve oxygenation, and allow the fetus to survive closer to term. Maternal complications, such as hypertension or the onset of mirror syndrome, are closely monitored and may necessitate immediate delivery.
Delivery planning for a severely affected fetus is orchestrated at a tertiary care center equipped for high-risk neonates. The plan addresses the timing and method of delivery, as well as immediate postnatal care requirements. After birth, the infant requires immediate and chronic blood transfusions, and families may explore curative long-term treatments, such as hematopoietic stem cell transplantation.