Prenatal Workup for Thalassemia
Screen both partners with complete blood count (CBC) focusing on mean corpuscular volume (MCV), and if either partner has MCV <80 fL, proceed with hemoglobin analysis to identify carriers, followed by prenatal diagnosis if both are carriers.
Initial Maternal Screening
All pregnant women should undergo CBC screening with particular attention to MCV, as thalassemia carriers typically have MCV values below 80 fL and often below the 5th percentile for age 1, 2, 3.
Red blood cell count is typically normal or elevated in thalassemia trait, which helps distinguish it from iron deficiency anemia where RBC count is usually low 2, 3.
Red blood cell distribution width (RDW) ≤14.0% suggests thalassemia trait, while RDW >14.0% suggests iron deficiency anemia 2, 3.
Measure serum ferritin to exclude concurrent iron deficiency, as iron deficiency can mask thalassemia trait characteristics and falsely lower HbA2 levels 2.
Critical Pitfall to Avoid
- If iron deficiency is present (ferritin below reference range), provide iron replacement therapy before performing hemoglobin analysis, as iron deficiency can falsely lower HbA2 levels and mask the diagnosis of beta-thalassemia trait 2.
Partner Screening
When the pregnant woman is identified as a thalassemia carrier, partner screening is mandatory to determine if the couple is at risk for having an affected child 1.
Partner screening should include CBC with MCV measurement, and if MCV <80 fL, proceed with hemoglobin analysis 1.
In clinical practice, non-compliance with partner screening occurs in approximately 34% of cases, often due to partner reluctance or lack of understanding of the importance 4.
Prenatal Diagnosis for At-Risk Couples
When both partners are carriers, offer prenatal diagnosis through:
Chorionic villus sampling (CVS) at 10-13 weeks gestation for DNA-based testing to detect common deletions or point mutations 1, 4, 5.
Amniocentesis at 15-20 weeks gestation as an alternative to CVS for DNA analysis 1.
Fetal blood sampling (cordocentesis) can evaluate for abnormal Bart's hemoglobin in alpha thalassemia, though this is less commonly used than DNA-based methods 1.
Alpha Thalassemia-Specific Considerations
Alpha thalassemia is the most common cause of non-immune hydrops fetalis, particularly in Southeast Asian populations where it accounts for 28-55% of cases 1, 3.
DNA testing for alpha-thalassemia should be performed when parental MCV is <80 fL in the workup of non-immune hydrops fetalis 1.
Ultrasound surveillance in the late second and early third trimester can detect hydrops fetalis in severe alpha thalassemia (Bart's hydrops syndrome) 1.
Genetic Counseling Requirements
Provide clear, nondirective counseling covering: the name and characteristics of the carrier state, the disease the baby could be at risk for, characteristics of the disease, risks to the child, and options including no further action or prenatal diagnosis 1.
Emphasize that if the partner is negative, the couple will be reassured, whereas if both are carriers, they face a 25% risk with each pregnancy of having an affected child 1.
Explain that prenatal diagnosis results will inform the couple's decision about continuing or terminating the pregnancy, but the decision is entirely theirs 1.
Alternative Options
- Preimplantation genetic diagnosis (PGD) is available for couples at risk who wish to avoid prenatal diagnosis and potential pregnancy termination 6.
Follow-Up After Prenatal Diagnosis
If prenatal diagnosis shows an affected fetus, provide comprehensive counseling about the severity of the condition, treatment options (lifelong transfusions, iron chelation, potential bone marrow transplantation), and the option of pregnancy termination 7, 8.
If the fetus is unaffected or a carrier only, provide reassurance and document results for future pregnancies 4, 5.