• Differential diagnosis for symmetric Intrauterine Growth Restriction (IUGR).
• Evaluation of fetal anomalies on ultrasound (e.g., intracranial calcifications, microcephaly, hydrops).
• Screening pregnant patients with concerning exposures or viral prodromes (fever, lymphadenopathy, rash).
• Workup for unexplained stillbirth or neonatal jaundice/thrombocytopenia.

These agents share the ability to cross the placenta (hematogenous spread) or infect the fetus via the birth canal (ascending/contact spread). The severity of fetal impact is generally inversely proportional to the gestational age at the time of primary maternal infection.

• CMV: The most common congenital infection; look for periventricular calcifications on US.
• Toxoplasmosis: Classically presents with the triad of chorioretinitis, hydrocephalus, and intracranial calcifications (diffuse, unlike CMV).
• Syphilis: Rising incidence; check RPR/VDRL at first visit and again at 28 weeks in high-risk areas.
• HSV: Risk of transmission is highest (30–50%) during a primary outbreak at the time of delivery; recurrent outbreaks carry <1% risk.

• IgM false positives are common; always confirm with IgG avidity testing if available.
• Low IgG avidity suggests a primary infection within the last 3–4 months.
• Do not wait for seroconversion in HSV; if lesions are present, treat empirically and consider C-section.

• Determine timing of infection via IgG avidity or serial titers.
• Refer to Maternal-Fetal Medicine (MFM) for detailed anatomy ultrasound.
• Consider amniocentesis for PCR (wait at least 6-8 weeks post-infection and after 21 weeks gestation for CMV).
• Initiate pathogen-specific therapy (e.g., Spiramycin/Pyrimethamine for Toxo, Penicillin for Syphilis).

The acronym was coined in 1971 by André Nahmias to group infections that presented with similar clinical features in the neonate. While the "Other" category has expanded significantly, the framework remains the primary teaching tool for perinatal infectious diseases.