What is the recommended screening process for thalassemia (a genetic disorder) in a fetus?

Recommended Screening Process for Thalassemia in a Fetus

The recommended screening process for thalassemia in a fetus should begin with carrier screening of both parents, ideally before conception or as early as possible in pregnancy, followed by prenatal diagnosis through chorionic villus sampling or amniocentesis if both parents are carriers. 1

Parental Carrier Screening Algorithm

Step 1: Identify At-Risk Populations

• Screen women and their partners who belong to ethnic populations with higher carrier rates:
  • Mediterranean (Greek, Italian, Cypriot)
  • Middle Eastern
  • South Asian
  • Southeast Asian
  • African or African-American (for hemoglobinopathies)
  • Chinese (particularly for alpha-thalassemia)

Step 2: Initial Maternal Screening

• Complete blood count (CBC)
• Hemoglobin electrophoresis or high-performance liquid chromatography (HPLC)
• Quantitation of HbA2 and HbF
• If microcytosis (MCV < 80 fL) or hypochromia (MCH < 27 pg) is present with normal electrophoresis:
  • Perform brilliant cresyl blue stained blood smear to identify H bodies
  • Check serum ferritin to exclude iron deficiency anemia 1

Step 3: Partner Screening

• If maternal screening is abnormal (showing microcytosis, hypochromia, elevated HbA2, or variant hemoglobin), screen the partner using:
  • Complete blood count
  • Hemoglobin electrophoresis or HPLC
  • HbA2 and HbF quantitation
  • H body staining 1

Prenatal Diagnosis for At-Risk Pregnancies

Step 4: Genetic Counseling

• If both parents are carriers, refer for genetic counseling
• Additional molecular studies may be needed to clarify carrier status and fetal risk 1

Step 5: Prenatal Diagnosis Options

1. DNA-based diagnosis:

   • Chorionic villus sampling (CVS) at 10-13 weeks gestation
   • Amniocentesis at 15-18 weeks gestation
   • PCR amplification and mutation analysis 2, 3

2. For couples declining invasive testing who are at risk for hemoglobin Bart's hydrops fetalis:

   • Serial detailed fetal ultrasound to assess cardiothoracic ratio (normal < 0.5)
   • Referral to tertiary care center if abnormalities detected
   • Confirmatory DNA analysis if pregnancy termination is considered 1

Special Considerations

• Timing: Ideally, screening should occur pre-conceptionally to allow more time for decision-making and reduce psychological distress 1
• Hydrops fetalis: If detected on ultrasound in second or third trimester in at-risk populations, immediately investigate parents for alpha-thalassemia carrier status 1
• Advanced techniques: In specialized centers, preimplantation genetic diagnosis (PGD) may be offered as an alternative to traditional prenatal diagnosis 4

Pitfalls to Avoid

• Incomplete screening: Always screen both parents if one is identified as a carrier
• Misinterpretation of iron deficiency: Iron deficiency can mask beta-thalassemia trait by lowering HbA2 levels
• Delayed screening: Screening late in pregnancy limits options and increases psychological distress
• Inadequate counseling: Ensure couples understand the implications of carrier status and the available options for prenatal diagnosis

Carrier screening and prenatal diagnosis programs have proven highly effective in reducing the incidence of thalassemia major in at-risk populations through education and acceptance of screening 5. The combination of hematological screening and molecular diagnostic techniques provides reliable results for prenatal diagnosis of thalassemia 3.