Prenatal Workup for Thalassemia

Initial Maternal Screening

The American College of Obstetricians and Gynecologists recommends that 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.

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.

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 4, 5, 6, 7, 8.
Partner screening should include CBC with MCV measurement, and if MCV <80 fL, proceed with hemoglobin analysis 1, 9, 10.

Chorionic villus sampling (CVS) at 10-13 weeks gestation can be used for DNA-based testing to detect common deletions or point mutations 1.
Amniocentesis at 15-20 weeks gestation can be used as an alternative to CVS for DNA analysis 1, 9, 10.
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, 9.

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, 9, 3.
DNA testing for alpha-thalassemia should be performed when parental MCV is <80 fL in the workup of non-immune hydrops fetalis 1, 9, 10.
Ultrasound surveillance in the late second and early third trimester can detect hydrops fetalis in severe alpha thalassemia (Bart's hydrops syndrome) 1, 9.

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 4, 5, 6, 7, 8.
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 4, 5, 6, 7, 8.
Explain that prenatal diagnosis results will inform the couple's decision about continuing or terminating the pregnancy, but the decision is entirely theirs 4, 5, 6, 7, 8.

Alpha thalassemia carriers with two-gene deletions have a risk of producing a child with Hemoglobin Bart's hydrops fetalis, a typically fatal condition, if both parents carry the same mutation 11, 12
The American College of Obstetricians and Gynecologists acknowledges that beta thalassemia carriers have a risk of producing a child with beta thalassemia major, requiring lifelong blood transfusions and significant medical management 11

Genetic counseling should be provided in a clear, nondirective manner, covering the carrier state characteristics, disease risks, and all available options, as recommended by the American Society of Human Genetics 13
Consideration of ethnicity is crucial in risk assessment, as alpha thalassemia is most common in Southeast Asian populations, while beta thalassemia predominates in Mediterranean, Middle Eastern, and South Asian populations 11