TORCH Screen

The TORCH screen is a panel of IgM and IgG serology for infections that cause congenital disease: Toxoplasma gondii, Rubella virus, Cytomegalovirus, Herpes simplex virus and other agents (syphilis, varicella zoster virus, parvovirus B19, Zika virus, HIV and lymphocytic choriomeningitis virus in extended panels).

It is used when a foetus or newborn has findings suggestive of congenital infection (growth restriction, microcephaly, intracranial calcification, hydrops, hepatosplenomegaly, jaundice, thrombocytopenia, chorioretinitis, cataract, deafness, heart defects).

Each component is interpreted with the clinical picture, and PCR on the infant's blood, urine, saliva, CSF or on amniotic fluid is usually more informative than serology.

Congenital infection affects about 1 to 3% of newborns worldwide (CMV 0.5 to 1%, toxoplasmosis 0.1 to 0.5%, syphilis varies from under 0.01% to over 1% in some regions, herpes 0.01%, rubella is now rare where vaccination is universal). Many infected infants are asymptomatic at birth and present later with hearing loss, visual impairment or neurodevelopmental delay. Routine TORCH panels in unselected pregnancies or neonates have a low yield and many false positives, so testing is targeted.

Components.

• Toxoplasma IgG and IgM. IgG avidity distinguishes infection within the last 3 to 4 months (low avidity) from older infection.
• Primary infection in pregnancy transmits to the foetus in 15% in the first trimester, 30% in the second and 60% near term, with severity highest early.
• Neonatal diagnosis uses IgM, IgA and persistent IgG after 12 months, with PCR of amniotic fluid, blood or CSF.
• Rubella IgG and IgM. Congenital rubella syndrome follows infection in the first 16 weeks. Infant IgM positive, or IgG persisting beyond 6 to 9 months, or PCR of throat swab, urine or CSF, confirms infection.
• CMV IgG, IgM and avidity. Congenital CMV is confirmed by CMV DNA PCR of urine, saliva or blood in the first 3 weeks of life, or on the neonatal dried blood spot. Serology is secondary.
• HSV IgG and IgM. Neonatal herpes is diagnosed by PCR of vesicle, blood, CSF, conjunctiva, mouth and rectal swabs. Serology has little role.
• Syphilis (treponemal and non-treponemal tests). Maternal serology at booking, with infant testing and clinical examination if maternal infection is untreated or inadequately treated.
• Other agents. Varicella zoster, parvovirus B19, Zika (RNA, IgM with neutralisation tests), HIV, lymphocytic choriomeningitis virus and Chagas disease in endemic areas.

Indications. Foetal ultrasound abnormalities (microcephaly, ventriculomegaly, periventricular calcification, hydrops, echogenic bowel, growth restriction). Newborn with petechiae, jaundice, hepatosplenomegaly, microcephaly, seizures, chorioretinitis, cataract, congenital heart disease, deafness or small for gestational age. Maternal illness with fever and rash in pregnancy.

Recurrent miscarriage and stillbirth workup (selected agents only). Infants failing newborn hearing screening. Not for routine screening of asymptomatic healthy women.

Specimen.

• Maternal serum 2 to 3 mL (a paired sample 2 to 3 weeks apart when needed).
• Infant serum or cord blood 1 mL (not contaminated with maternal blood), urine 2 to 5 mL, saliva swab and CSF 1 mL.
• Amniotic fluid 10 to 20 mL obtained after 18 to 21 weeks and 6 weeks after maternal infection.

Dried blood spots from the newborn screening card may be kept for retrospective CMV and toxoplasma PCR.

Reference values. All IgM and DNA tests are negative in healthy people. IgG is positive in people immune to the infection (toxoplasma 10 to 30% of adults in low prevalence countries and over 50 to 80% in high prevalence regions; rubella over 90% in vaccinated populations; CMV 50 to 90%).

Pattern interpretation.

• Infant IgM antibody is not transferred across the placenta, so a positive IgM in cord or neonatal blood suggests congenital infection. Sensitivity is only 50 to 70% for CMV, toxoplasma and rubella, and false positive results occur from maternal blood contamination, rheumatoid factor and cross-reactions.
• Persistent infant IgG beyond 12 months (when maternal antibody is gone) confirms congenital infection with toxoplasmosis and rubella. Falling infant IgG over 6 to 12 months suggests passive transfer.
• Amniotic fluid PCR has sensitivity of 90% for toxoplasma and CMV after the right timing, and a negative result earlier than 18 to 21 weeks does not exclude infection.
• A single positive component with an otherwise normal infant requires repeat testing and clinical correlation.
• A negative panel does not exclude congenital infection from other causes (genetic, toxic, metabolic).

Critical values and findings needing immediate action.

• Newborn with a rash, hepatosplenomegaly, jaundice, thrombocytopenia and positive syphilis serology: congenital syphilis, urgent treatment with penicillin and CSF examination.
• Maternal primary toxoplasma infection confirmed in pregnancy: immediate treatment (spiramycin for prevention of transmission, pyrimethamine sulphadiazine with folinic acid if foetal infection is proven) and specialist foetal medicine referral.
• Neonate with seizures, microcephaly, chorioretinitis or intracranial calcification: urgent infection workup, cranial imaging, ophthalmology, and treatment (valganciclovir for symptomatic CMV, aciclovir for herpes).
• Neonate with vesicles, fever or lethargy in the first 4 weeks: intravenous aciclovir while awaiting PCR.
• Infant with abnormal hearing screen: CMV PCR on saliva or urine within 21 days of birth.

Interferences and pitfalls.

• Broad TORCH panels give a high false positive rate and low yield. Testing should be directed by clinical findings and the likely agent.
• IgM can persist for months to years (toxoplasma IgM can remain positive for over a year), so a positive result does not date the infection. Avidity and paired samples are needed.
• Maternal IgG in the infant can persist for 9 to 12 months and does not show infection.
• Cord blood is contaminated with maternal blood more often than peripheral infant blood.
• Maternal immunosuppression (HIV, transplant) can produce atypical serology.
• Serology cannot be used for congenital CMV without PCR confirmation in the first 3 weeks, because later positive results may be postnatal.
• Syphilis serology may be negative in early infection and in the infant, so the maternal history, treatment and clinical findings are reviewed.
• Rubella reinfection after vaccination gives IgM positivity with low risk to the foetus.
• Herpes simplex serology does not predict neonatal herpes, and maternal lesions at delivery are the main risk.

Special groups.

• Pregnant women: the highest risk time for severe disease is early gestation. Prevention counselling includes hand hygiene, avoiding undercooked meat, cat litter and unwashed vegetables (toxoplasma), avoiding saliva sharing with toddlers (CMV), and safer sex.
• Newborns: infected infants need follow up for hearing, vision and development up to school age.
• Immunocompromised mothers: reactivation of toxoplasma and CMV can transmit to the foetus.
• Regions: congenital syphilis and toxoplasmosis remain common in low income countries, malaria and Chagas disease are additional causes of congenital infection in endemic areas, and Zika virus testing is added for exposure in affected regions.

Follow up tests.

• CMV, toxoplasma and rubella PCR in infant samples, IgG avidity, paired maternal and infant serology.
• Syphilis treponemal tests and VDRL or RPR titres.
• CSF analysis, cranial ultrasound or MRI, ophthalmology examination, auditory brainstem response.
• Full blood count, liver function tests, echocardiography.
• Foetal ultrasound and amniocentesis, and repeat IgG at 12 months.