What is IgG (Immunoglobulin G) avidity testing in the context of a pregnant woman with a history of CMV (Cytomegalovirus) and rubella exposure?

IgG Avidity Testing

IgG avidity testing measures the strength with which IgG antibodies bind to viral antigens, and it matures gradually over 6 months following primary infection—making it a highly sensitive and specific method to distinguish recent primary CMV or rubella infection from past infection in pregnant women. 1

What Avidity Measures

• Avidity refers to the binding strength between IgG antibodies and antigenic epitopes on viral proteins 1
• During primary infection, IgG antibodies initially bind weakly (low avidity), then gradually mature to bind more strongly (high avidity) over approximately 6 months 1
• This maturation process creates a diagnostic window that allows clinicians to estimate when the primary infection occurred 1

Clinical Interpretation in Pregnancy

Low Avidity Results

• Low CMV IgG avidity (typically <35-50% depending on assay) indicates primary infection occurred within the preceding 3-4 months 1, 2, 3
• Low avidity with positive IgM at ≤14 weeks gestation has 83.3% sensitivity and 83.8% specificity for identifying congenital CMV infection risk 2
• 98.8% of low-avidity samples correspond to infection onset within 180 days before sampling 4

High Avidity Results

• High CMV IgG avidity (typically >50-60% depending on assay) excludes primary infection within the preceding 3 months 1, 3
• 77.8% of high-avidity results correspond to infection onset >90 days before sampling 4
• High avidity in pregnant women indicates past infection with low risk of congenital transmission 5, 6

When to Order Avidity Testing

• The American College of Obstetricians and Gynecologists recommends IgG avidity testing when both CMV IgG and IgM are positive in pregnant women 5
• Avidity testing resolves the diagnostic dilemma created by persistent IgM, which can remain positive for months after primary infection or appear during reactivation 1
• The test is most useful when performed early in pregnancy or soon after suspected exposure, as it becomes less discriminatory later in gestation 2

Diagnostic Algorithm for Pregnant Women

1. Initial screening: Order CMV IgG and IgM 7
2. If IgG negative: Patient is susceptible; counsel on prevention 7
3. If IgG positive alone: Past infection with immunity; low risk of congenital transmission 5, 6
4. If both IgG and IgM positive: Order IgG avidity testing immediately 5
   • Low avidity = recent primary infection (high risk for fetal transmission) 1, 2
   • High avidity = past infection with false-positive or persistent IgM (low risk) 1, 3

Relationship Between IgM Levels and Avidity

• Strong CMV IgM reactivity (index ≥3.0) correlates with low avidity in 93-94% of cases 3
• However, IgM alone has poor specificity because it persists after primary infection and appears during reactivation 1
• The combination of positive IgM with low avidity at ≤14 weeks gestation provides 99.1% negative predictive value for congenital infection 2

Assay-Specific Considerations

• Different commercial assays use varying cutoff values for low versus high avidity 4, 3
• The Elecsys CMV IgG Avidity assay shows 90-97% sensitivity and 89-100% specificity depending on how gray-zone values are handled 4
• Some assays define low avidity as <35% 2, while others use <50% 3
• Always interpret results according to the specific assay's validated cutoffs 4

Critical Timing Limitations

• Avidity testing is only useful when performed at the appropriate time—it cannot detect primary infection if measured too late after seroconversion 2
• Low IgG avidity loses its predictive value for congenital infection when measured at ≥15 weeks gestation 2
• The 6-month maturation window means that by late pregnancy, most primary infections will show high avidity 1

Common Pitfalls to Avoid

• Do not assume negative IgM rules out recent infection—order avidity testing if clinical suspicion remains high despite negative IgM 5
• Do not rely on avidity testing alone in late pregnancy—it becomes less discriminatory after the first trimester 2
• Do not interpret avidity results without knowing the specific assay's cutoff values—thresholds vary between manufacturers 4, 3
• Do not delay amniocentesis in pregnant women with fetal abnormalities based on negative maternal IgM alone—fetal infection can occur with maternal reactivation 5