Is avidity testing for Rubella (German measles) valid during pregnancy, especially in a woman with a history of rubella exposure?

Rubella Avidity Testing During Pregnancy

Yes, rubella IgG avidity testing is valid and clinically useful during pregnancy to distinguish recent primary infection from past infection or reinfection, which is critical for assessing fetal risk. 1, 2

Clinical Utility and Validity

Avidity testing is specifically designed to address the diagnostic challenge in pregnant women when rubella IgM antibodies are detected, as it helps differentiate between:

• Recent primary infection (low avidity IgG) - poses significant risk to the fetus
• Past infection or reinfection (high avidity IgG) - minimal to no fetal risk 1, 2

The test is based on the principle that chaotropic agents selectively dissociate low-avidity antibodies generated early in infection while leaving high-affinity IgG1 responses from past infections relatively unaffected. 1

Interpretation Timeline

Low avidity IgG (avidity index <40%):

• Indicates infection within the past 6 weeks from onset of rash
• Confirms recent primary infection when IgM is positive
• Warrants counseling about congenital rubella syndrome risk 3

High avidity IgG (avidity index >60%):

• Not observed until at least 13 weeks post-infection
• Effectively excludes recent primary infection
• Reassures that any IgM detected is likely persistent, non-specific, or from remote infection 3

Intermediate avidity (40-60%):

• Requires repeat testing in 2-3 weeks or additional immunoblot analysis
• May need E2-specific IgG testing for further clarification 2

Clinical Context and Importance

The validity of avidity testing during pregnancy is particularly important because:

• Rubella directly infects the fetal brain causing neuronal death, gliosis, and disrupted mitosis 4
• Primary rubella infection during pregnancy, especially in the first trimester, carries substantial risk for congenital rubella syndrome 5
• The proportion of non-specific IgM reactivity has increased as rubella incidence has declined, making avidity testing essential for accurate diagnosis 3
• Asymptomatic primary rubella infections do occur and can result in congenital rubella syndrome, while reinfections (with high avidity) pose minimal fetal risk 6

Diagnostic Algorithm

When rubella IgM is detected in a pregnant woman:

1. Immediately perform IgG avidity testing 1, 2
2. If low avidity (<40%): Confirm recent primary infection; counsel regarding congenital rubella syndrome risk and consider detailed fetal ultrasound 2-4 weeks after maternal illness onset 4
3. If high avidity (>60%): Exclude recent primary infection; reassure patient that fetal risk is minimal 3
4. If intermediate avidity: Consider glycoprotein-based IgM ELISA (92.3% specificity vs 80.8% for whole-virus antigen) and E2-specific IgG immunoblot analysis to determine timing more precisely 2

Important Caveats

• Avidity testing requires appropriate antigens; glycoprotein-based assays provide superior specificity (92.3%) compared to whole-virus lysate assays (80.8%) for distinguishing true infection from cross-reactive IgM in patients with other acute infections 2
• The avidity index increases steadily over months, with most pronounced changes in the first 3 months post-infection 3
• Combining avidity testing with E2-specific IgG immunoblot analysis allows unambiguous determination of infection timing in >86% of cases 2
• In a Ghanaian study of 145 pregnant women, 3.4% had low avidity antibodies, demonstrating the ongoing relevance of this testing even in vaccinated populations 7