Can alpha thalassemia be diagnosed in a fetus during pregnancy?

Prenatal Diagnosis of Alpha Thalassemia During Pregnancy

Yes, alpha thalassemia can be diagnosed in a fetus during pregnancy through both invasive and non-invasive prenatal testing methods. The diagnosis is critical since alpha thalassemia major (Hb Bart's hydrops fetalis) can lead to severe fetal anemia, hydrops fetalis, and fetal death.

Screening Process for Alpha Thalassemia

Initial Maternal Screening

• Screen pregnant women using complete blood count (CBC) with red cell indices
  • Look for low mean corpuscular volume (MCV < 80 fL)
  • Look for low mean cell hemoglobin (MCH < 27 pg)
• If low red cell indices are found, proceed with hemoglobin electrophoresis and iron studies to rule out iron deficiency 1
• For populations with high prevalence of alpha thalassemia (particularly Southeast Asian), screen the father as well 2

Risk Assessment

• If both parents have low MCV/MCH consistent with possible alpha thalassemia trait, consider them at risk for having a fetus with alpha thalassemia major
• Alpha thalassemia is particularly common in Southeast Asian populations, where it accounts for 28-55% of non-immune hydrops fetalis cases 2

Diagnostic Testing Options

Invasive Prenatal Testing (Gold Standard)

1. Amniocentesis (performed at 16-18 weeks)

   • DNA testing for alpha thalassemia deletions or mutations
   • Provides definitive diagnosis 2, 1

2. Chorionic Villus Sampling (CVS) (performed at 10-13 weeks)

   • Earlier diagnosis than amniocentesis
   • DNA analysis for alpha thalassemia mutations

3. Fetal Blood Sampling

   • Can be performed if intrauterine transfusion is planned
   • Can detect abnormal Bart's hemoglobin 2

Non-Invasive Approaches

1. Cell-free Fetal DNA Testing

   • Detection of paternal mutations in maternal plasma
   • Newer techniques include analysis of proportion of wild and mutant alleles
   • Currently considered experimental but promising 3

2. Ultrasound Screening

   • Monitor for signs of fetal anemia or hydrops fetalis
   • Measurement of cardiothoracic ratio can be a good screening tool for alpha thalassemia major 1
   • Middle cerebral artery Doppler peak systolic velocity (MCA PSV) to detect fetal anemia (PSV >1.5 MoM suggests anemia) 2

Management Algorithm

1. Initial Screening:

   • Test maternal MCV and MCH during first trimester prenatal visit
   • If MCV < 80 fL or MCH < 27 pg, proceed with hemoglobin electrophoresis

2. Partner Testing:

   • If mother is a suspected carrier, test the father's MCV and MCH
   • If father also has low indices, proceed to genetic counseling

3. Genetic Counseling:

   • Discuss risk of alpha thalassemia major
   • Explain diagnostic options and their risks/benefits

4. Prenatal Diagnosis:

   • Offer invasive testing (CVS or amniocentesis) for definitive diagnosis
   • Consider non-invasive monitoring with ultrasound and MCA Doppler
   • For high-risk cases, consider newer non-invasive prenatal testing methods if available

Important Considerations and Pitfalls

• Risk of Invasive Testing: Amniocentesis and CVS carry a small risk of pregnancy loss (approximately 0.1-0.3%)
• False Negatives: Some alpha thalassemia mutations may be missed if they are rare or not included in standard testing panels
• Ultrasound Limitations: Hydrops fetalis typically presents in late second or early third trimester, so early ultrasound may miss affected fetuses
• Ethnic Considerations: Testing strategies should be tailored based on the prevalence of specific mutations in the couple's ethnic background
• Timing: Early diagnosis is critical as alpha thalassemia major can lead to severe complications including fetal death

Alpha thalassemia screening and diagnosis should be prioritized in populations with high prevalence, particularly those of Southeast Asian descent, where carrier rates can be as high as 30-40% 2.