How should fetal anemia be diagnosed in a pregnant patient with risk factors such as alloimmunization, maternal infection, twin‑twin transfusion, or placental insufficiency, or with unexplained fetal hydrops or growth restriction?

Diagnosis of Fetal Anemia

Middle cerebral artery peak systolic velocity (MCA-PSV) is the primary and recommended diagnostic screening tool for fetal anemia in all at-risk pregnancies, with fetal blood sampling reserved for confirmation when MCA-PSV exceeds 1.5 multiples of the median (MoM). 1

Primary Screening Method: MCA-PSV Doppler

MCA-PSV should be used as the first-line screening technique for detecting fetal anemia, regardless of the underlying cause (alloimmunization, parvovirus infection, twin-twin transfusion syndrome, fetomaternal hemorrhage, or placental insufficiency). 1

Diagnostic Performance

• Sensitivity approaches 100% (95% CI: 0.86-1.0) for detecting moderate to severe fetal anemia 1, 2
• False-positive rate is approximately 12% with single measurements 1
• Serial MCA-PSV measurements (trend analysis) reduce the false-positive rate to less than 5%, making this approach superior to single measurements 1, 3
• A pooled meta-analysis demonstrated 75.5% sensitivity and 90.8% specificity for severe anemia detection 1

Critical Threshold

MCA-PSV >1.5 MoM indicates significant risk for severe fetal anemia and warrants proceeding to fetal blood sampling with preparation for intrauterine transfusion. 1, 3

Proper MCA-PSV Measurement Technique

Accurate measurement requires strict adherence to standardized technique to avoid false results:

• Anatomical location: Measure the proximal MCA approximately 2 mm distal to its origin from the internal carotid artery (intraclass correlation 0.98-0.99 for reproducibility) 3
• Imaging plane: Obtain an axial view at the level of the sphenoid bones to visualize the circle of Willis with color Doppler; zoom so the entire MCA length occupies >50% of the image 3
• Beam alignment: Align the ultrasound beam as close to 0° as possible, parallel to the vessel along its full length; avoid angle correction as this leads to overestimation 1, 3, 4
• Fetal state: Acquire measurements only during fetal quiescence (no breathing or body movements) to minimize heart rate-related velocity variability 3
• Replication: Perform at least three consecutive measurements and record the highest value for clinical decision-making 3
• Examination time: The complete assessment requires approximately 5-10 minutes when performed by trained personnel 3

Definitive Diagnosis: Fetal Blood Sampling

Fetal blood sampling (cordocentesis) provides the definitive diagnosis of fetal anemia and should be performed when: 1

• MCA-PSV exceeds 1.5 MoM 1
• Fetal hydrops is present 1
• Preparation for intrauterine transfusion is needed 1

Laboratory Evaluation After Cordocentesis

When fetal blood is obtained, comprehensive testing should include: 5

• Complete blood count with hemoglobin and hematocrit
• Blood morphology and red cell indices
• Reticulocyte count
• Blood group typing (mother and fetus)
• Hemoglobin typing and screening for hemoglobinopathies
• Parvovirus B19 serology
• TORCH titers (toxoplasmosis, rubella, cytomegalovirus, herpes simplex, HIV, syphilis)
• Acid elution test (for fetomaternal hemorrhage)

What NOT to Use

Amniotic fluid delta optical density 450 (ΔOD450) should NOT be routinely used to diagnose fetal anemia, as MCA-PSV has superior diagnostic accuracy. 1, 3

Umbilical artery Doppler does NOT reliably detect fetal anemia because it primarily reflects placental resistance rather than fetal hemoglobin status; it is appropriate for assessing placental insufficiency and growth restriction, not anemia. 3

Surveillance Protocol for At-Risk Pregnancies

MCA-PSV assessment should be reserved for patients at risk for fetal anemia, not performed universally. 1

Specific Risk Categories and Monitoring

For alloimmunization: 1

• Perform fetal antigen testing (cell-free fetal DNA for Rh-D or amniocentesis for genotyping) once critical antibody titer is reached
• If fetus is antigen-positive, initiate weekly MCA-PSV surveillance
• Serial antibody titers every 4 weeks, more frequently if rising or with advancing gestational age

For parvovirus exposure: 1

• Confirm maternal antibody status (IgM positive or IgG seroconversion)
• Peak risk for hydrops occurs 4-6 weeks after maternal infection
• Perform weekly MCA-PSV and ultrasound surveillance for fetal hydrops for 10-12 weeks after exposure

For twin-twin transfusion syndrome: 1

• MCA-PSV is applicable for detecting anemia in the donor twin

For unexplained hydrops or growth restriction: 1

• MCA-PSV screening helps identify occult fetal anemia from various causes

Referral and Management Thresholds

Refer to a tertiary care center with expertise in invasive fetal therapy when: 1, 4

• MCA-PSV exceeds 1.5 MoM
• Fetal hydrops is detected
• Intrauterine transfusion may be required

Fetal blood sampling with preparation for intrauterine transfusion should be offered unless the pregnancy has reached a gestational age where delivery risks are lower than procedural risks (typically >34-35 weeks). 1, 4

Common Pitfalls and Caveats

• Approximately 10% of elevated MCA-PSV results are false positives (fetuses are not severely anemic), necessitating confirmatory fetal blood sampling before intervention 1, 4
• Improper technique leads to overestimation: Measuring too distal in the MCA, using excessive angle correction, or measuring during fetal movement all produce falsely elevated values 1, 3
• Operator training is essential: Inexperienced sonographers produce unreliable results; patients should be referred to centers with certified personnel 3
• Standard thalassemia screening tests (osmotic fragility, DCIP) do NOT detect hemoglobin variants such as Constant Spring or Pakse, which can cause severe fetal anemia and hydrops 5

Delivery Timing

Plan delivery at 37-38 weeks of gestation for pregnancies with a fetus at risk for anemia, unless complications develop requiring earlier intervention. 1, 4