Is IgG avidity testing valid for a 22-week pregnant woman with positive Immunoglobulin G (IgG) for Rubella and Cytomegalovirus (CMV)?

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IgG Avidity Testing at 22 Weeks Gestation

IgG avidity testing remains valid and clinically useful at 22 weeks gestation for both rubella and CMV when IgG is positive, but its interpretation differs significantly between the two infections and depends critically on when maternal infection occurred relative to conception.

CMV IgG Avidity Testing at 22 Weeks

Validity and Clinical Utility

  • CMV IgG avidity testing is valid at 22 weeks gestation and should be performed when both IgG and IgM are positive to help determine timing of maternal infection 1

  • Low CMV IgG avidity accurately indicates primary infection within the preceding 3-4 months, while high avidity excludes primary infection within the preceding 3 months 2

  • IgG avidity matures gradually during the 6 months following primary CMV infection, making it both sensitive and specific for identifying recent primary infection 2

Critical Limitations at 22 Weeks

  • A negative CMV IgM in the second trimester (including 22 weeks) cannot exclude congenital CMV infection, as documented cases of congenital CMV have occurred despite negative second-trimester maternal IgM 3

  • CMV IgG avidity testing has reduced discriminatory power when performed late in pregnancy, as the avidity may have already matured to high levels even if infection occurred periconceptionally 3, 4

  • In cases where infection occurred around conception or early first trimester, by 22 weeks the IgG avidity may already be high, potentially missing the window for accurate timing 3

Optimal Testing Strategy

  • Low IgG avidity combined with IgM positivity at ≤14 weeks gestation provides the best discrimination for congenital infection risk (sensitivity 83.3%, specificity 83.8%, negative predictive value 99.1%) 4

  • After 15 weeks gestation, low IgG avidity loses its value as an independent predictor of congenital infection in multivariate analysis 4

  • If stored first-trimester maternal blood samples are available, retrospective CMV serology and IgG avidity testing on those samples provides more valuable information than testing at 22 weeks 3

Rubella IgG Avidity Testing at 22 Weeks

Limited Clinical Utility

  • Rubella IgG avidity testing is technically valid at 22 weeks but has extremely limited clinical utility because rubella infection diagnosis requires acute-phase serum drawn within 7 days of rash onset 5

  • If the acute-phase serum specimen is drawn more than 7 days after rash onset, a significant rise in antibody titer may not be detected by most commonly used tests, making late-pregnancy testing unreliable 5

  • The Centers for Disease Control and Prevention recommends that prenatal serologic screening should be performed routinely early in pregnancy, with laboratories retaining specimens until delivery for potential retesting 5, 6

When Rubella Testing Is Indicated

  • Rubella serologic confirmation should only be pursued when there is documented rash illness or known exposure during pregnancy, with acute-phase serum obtained as soon as possible after rash onset (preferably within 7 days) 5

  • For pregnant women with positive rubella IgG alone at 22 weeks without documented acute illness, this simply indicates immunity and requires no further testing 6

Practical Algorithm for 22-Week Pregnant Woman

If CMV IgG Positive, IgM Negative:

  • Indicates past CMV exposure and immunity
  • Low risk of congenital CMV
  • No avidity testing needed 1

If CMV IgG Positive, IgM Positive:

  • Perform IgG avidity testing immediately 1
  • Low avidity suggests infection within past 3-4 months (high risk)
  • High avidity suggests infection >3 months ago (lower risk but does not exclude non-primary infection)
  • Proceed to amniocentesis for CMV PCR if avidity is low or if fetal abnormalities are present on ultrasound, performed at least 7 weeks after presumed maternal infection and after 21 weeks gestation 7

If Rubella IgG Positive Without Recent Rash/Exposure:

  • Indicates immunity
  • No further testing needed 6

If Rubella IgG Positive With Recent Rash (<7 Days):

  • Obtain acute-phase serum immediately
  • Convalescent-phase serum 10+ days later
  • Test for IgM and significant IgG rise 5

Common Pitfalls to Avoid

  • Do not assume negative CMV IgM at 22 weeks rules out congenital CMV infection, particularly if fetal abnormalities are detected on ultrasound 3

  • Do not rely solely on CMV IgG avidity results obtained late in pregnancy (after 15 weeks) to exclude periconceptional infection 4

  • Do not order rubella avidity testing at 22 weeks in the absence of documented acute illness or exposure, as positive IgG alone simply confirms immunity 6

  • For unexplained fetal abnormalities at 22 weeks with negative maternal CMV IgM, proceed directly to amniocentesis for CMV PCR rather than relying on serology alone 3

  • Perform detailed fetal ultrasound no sooner than 2-4 weeks after onset of suspected maternal CMV illness to allow time for fetal manifestations to develop 8

References

Guideline

Interpretation and Management of Positive CMV IgG Results

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Research

Maternal Cytomegalovirus (CMV) Serology: The Diagnostic Limitations of CMV IgM and IgG Avidity in Detecting Congenital CMV Infection.

Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society, 2024

Research

Maternal immunoglobulin G avidity as a diagnostic tool to identify pregnant women at risk of congenital cytomegalovirus infection.

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 2017

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Rubella Immunity and Titration Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Cytomegalovirus infection in pregnancy.

Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC, 2010

Guideline

Fetal Ultrasound Findings in Congenital CMV Infection

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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