What diagnostic tests are recommended for a couple in pregnancy at risk for Diamond-Blackfan anemia (Diamond-Blackfan anemia is a congenital hypoplastic anemia)?

Diagnostic Tests for Diamond-Blackfan Anemia in Pregnancy

For couples at risk for Diamond-Blackfan anemia (DBA) during pregnancy, a comprehensive diagnostic approach including genetic testing, ultrasound monitoring, and fetal blood sampling is recommended to assess fetal status and guide management.

Initial Assessment and Risk Evaluation

• Detailed family history to identify known inherited disorders and assess for consanguinity, which increases the likelihood of recessive disorders 1
• Maternal evaluation if she has DBA, as pregnancy may trigger relapse of anemia requiring increased frequency of blood transfusions 2, 3
• Prepregnancy counseling for parents with DBA to discuss inheritance patterns and pregnancy risks 4

Ultrasound-Based Surveillance

• Detailed fetal ultrasound to assess for:

  • Signs of fetal anemia or hydrops fetalis (fluid accumulation in fetal compartments) 1
  • Associated congenital anomalies, particularly radial ray defects which may be present in some DBA cases 5
  • Fetal growth parameters, as growth restriction may be present 5

• Middle cerebral artery (MCA) Doppler studies to screen for fetal anemia:

  • Peak systolic velocity (PSV) >1.5 MoM indicates severe anemia 1
  • This non-invasive test should be performed serially to monitor for developing anemia 1

• Fetal echocardiography to evaluate cardiac structure and function 1, 4

Invasive Diagnostic Testing

• Amniocentesis or chorionic villus sampling (CVS) for:

  • Karyotype analysis to rule out chromosomal abnormalities 1
  • Chromosomal microarray analysis (CMA) for more detailed genetic assessment 1
  • Specific DNA testing for DBA-associated mutations 1, 5

• Fetal blood sampling (cordocentesis) when indicated:

  • Direct measurement of fetal hemoglobin and hematocrit levels 1, 4
  • Should be considered when signs of anemia are present on ultrasound 4
  • Allows for potential therapeutic intervention (intrauterine transfusion) 4

Genetic Testing Approach

• Trio rapid whole-exome sequencing (rWES) has proven clinically useful in confirming DBA in both affected neonates and mothers 5
• Testing should include analysis of known DBA-associated genes, as DBA can follow both autosomal dominant and recessive inheritance patterns 6
• If the father is heterozygous for the implicated gene, fetal DNA obtained by amniocentesis may be required to determine fetal status 1

Management Considerations

• Serial monitoring with MCA Doppler and ultrasound throughout pregnancy to detect developing anemia or hydrops 1
• Consideration of intrauterine transfusions if severe fetal anemia develops 4
• Planning for potential early delivery if the fetus shows signs of compromise 4
• Multidisciplinary approach involving maternal-fetal medicine, hematology, and genetics 2

Common Pitfalls and Caveats

• DBA is a rare cause of fetal anemia, so other more common causes should be excluded first, including:

  • Immune causes (red blood cell alloimmunization)
  • Infectious causes (parvovirus B19, CMV, toxoplasmosis)
  • Other inherited anemias (alpha thalassemia, G6PD deficiency) 1

• False positive results can occur with MCA Doppler (approximately 10% false-positive rate), necessitating confirmation with invasive testing 1

• Pregnancy itself may worsen maternal DBA, requiring increased transfusion support 2, 3

• While most cases of DBA are diagnosed in infancy, prenatal manifestations can occur, including hydrops fetalis in severe cases 4, 5