TORCH is an acronym derived from the initials of a group of pathogens. These include Toxoplasma (T), Others (O, such as Treponema pallidum and human parvovirus B19), Rubella virus (R), Cytomegalovirus (C), and Herpes simplex virus (H). TORCH syndrome refers to the symptoms and signs observed in the perinatal period due to infections caused by these pathogens, such as miscarriage, stillbirth, preterm birth, and congenital abnormalities. Even if the fetus survives, there can be residual damage to the central nervous system or other complications. Pregnant women infected with TORCH pathogens are often asymptomatic or experience mild symptoms but may vertically transmit the infection to the fetus, resulting in intrauterine infection. This section primarily focuses on Toxoplasma (TOX), Rubella virus (RV), and Cytomegalovirus (CMV). Herpes simplex virus (HSV) can be seen in the section on "Genital Herpes."
Transmission Routes
Maternal Infection
Toxoplasma is often transmitted to pregnant women through the consumption of raw or undercooked meat containing cysts, unwashed vegetables or fruits, or contact with animal feces contaminated with oocysts (e.g., from cats).
Rubella virus is primarily transmitted through direct contact or respiratory droplets.
Cytomegalovirus can be transmitted via droplets, saliva, urine, sexual contact, blood transfusion, dialysis, or organ transplantation.
Maternal infection can be categorized into the following four types:
- Primary infection: The first encounter with a TORCH pathogen.
- Past infection: A history of symptomatic infection with a specific pathogen, or reliable serological evidence indicating a previous infection. The pathogen may either be completely eliminated by the immune system or persist in a latent state within the body.
- Reactivation: Reactivation of a latent pathogen in immunocompromised conditions.
- Reinfection: New infection caused by exposure to an exogenous strain of the same pathogen. Viral isolation and gene sequencing are often needed to confirm reinfection involving a new strain.
Vertical Transmission
Any TORCH pathogen can lead to fetal infection through the following routes:
- Intrauterine infection: Pathogens can reach the fetus—hematogenously via the placenta, ascending via the reproductive tract into the amniotic cavity, or externally through fetal membranes and then via the placenta.
- Birth canal infection: Pathogens can infect the fetus during delivery through the infected maternal genital tract.
- Postnatal infection: Newborns can be infected through maternal breast milk, saliva, or blood.
Impacts on Mother and Offspring
Effects on the Mother
Most pregnant women with TORCH infections are asymptomatic or experience mild symptoms. Some may present with nonspecific, flu-like symptoms such as low-grade fever, fatigue, arthralgia, myalgia, or localized lymphadenopathy. Rubella virus infection can lead to widespread maculopapular rash starting from the face and spreading to the trunk and limbs, often accompanied by joint pain or arthritis, cervical lymphadenopathy, and conjunctivitis.
Effects on the Fetus and Newborn
Pregnant women with primary infections may transmit the pathogen to the fetus via the placenta or birth canal. Infection at earlier gestational ages is associated with a higher risk and greater severity of congenital abnormalities.
Toxoplasmosis
The rate of intrauterine infection increases with gestational age, being 15% at 13 weeks, 44% at 26 weeks, and 71% at 36 weeks of pregnancy. However, early pregnancy infections have the most severe fetal consequences, often resulting in fetal death, miscarriage, or developmental defects, with a high likelihood of non-viability. Most newborns with congenital toxoplasmosis show no obvious symptoms at birth but may later develop hepatosplenomegaly, jaundice, anemia, intracranial calcifications, hydrocephalus, or microcephaly, as well as neurological disorders. Long-term complications include chorioretinitis and learning disabilities. Symptomatic infections in newborns are associated with a high incidence of long-term complications.
Rubella Virus Infection
More than 90% of fetuses are affected by intrauterine infection if the mother is infected within the first 12 weeks of gestation. The rate decreases to 54% at 13–14 weeks and 25% by the end of the second trimester. Infections occurring after 20 weeks of gestation generally do not lead to birth defects. Congenital rubella syndrome may involve one or multiple organ systems:
- Ocular defects: Congenital cataracts, glaucoma, microphthalmia, and pigmentary retinopathy.
- Congenital heart disease: Patent ductus arteriosus, pulmonary artery stenosis, ventricular septal defect, atrial septal defect, or tetralogy of Fallot.
- Sensorineural hearing loss: The most common single defect.
- Central nervous system abnormalities: Microcephaly, encephalitis, developmental delays, and intellectual disability.
Long-term sequelae may include diabetes mellitus, precocious puberty, and progressive panencephalitis.
Cytomegalovirus Infection
Intrauterine infection occurs in 30–40% of pregnant women with primary CMV infection but only in 0.15–2% of those with reactivation. Most affected newborns are asymptomatic at birth, although 5–15% exhibit symptoms, including intrauterine growth restriction, microcephaly, intracranial calcifications, hepatosplenomegaly, petechiae, jaundice, chorioretinitis, thrombocytopenic purpura, and hemolytic anemia. Long-term complications can include sensorineural hearing loss, visual impairment, neurological deficits, developmental delays, and learning disabilities.
Genital Herpes
Primary genital herpes infection during early and middle pregnancy poses minimal risk to the fetus, whereas late pregnancy infections may be associated with preterm birth and intrauterine growth restriction.
Clinical Manifestations and Diagnosis
Medical History and Clinical Manifestations
These include:
- A history of recurrent miscarriages, stillbirths, or congenital defects in newborns.
- A history of contact with pets before or during pregnancy, as well as habits such as consuming raw or undercooked meat.
- A history of exposure to rubella patients or a history of rashes or herpes lesions in one or both partners prior to or during pregnancy.
- Symptoms during pregnancy, such as fever or flu-like symptoms of an upper respiratory tract infection.
- Ultrasonographic findings of intrauterine abnormalities, such as fetal edema.
Laboratory Diagnosis
Pathogen Detection
Pathogen detection can be performed on maternal blood, urine, breast milk, amniotic fluid, umbilical cord blood, placenta, or newborn blood and urine. Methods include circulating antigen detection (for Toxoplasma), cytological examination (for CMV inclusion bodies), viral isolation (for RV and CMV), and nucleic acid amplification assays. Detection of specific DNA or RNA in amniotic fluid after 21 weeks of gestation and at least 6 weeks following maternal infection is the preferred method for diagnosing intrauterine infections.
Serological Testing
TOX, RV, and CMV-specific IgM and IgG antibodies in serum are tested. IgG avidity index is used to determine the maternal infection status:
- A seroconversion of IgG, IgM positivity, or low IgG avidity index with IgG positivity suggests primary infection; high IgG avidity index indicates reactivation of a past infection.
- Persistently elevated IgG antibody titers, combined with viral isolation and gene sequencing identifying a new viral strain, suggest reinfection.
- IgG positivity with IgM negativity indicates a past infection.
- TOX-specific IgA and IgE antibodies assist in diagnosing acute infections.
Imaging Studies
Ultrasound findings in fetuses with TORCH intrauterine infections are often nonspecific, with a sensitivity of approximately 15%. Repeated ultrasonographic examinations in the mid-to-late stages of pregnancy can reveal delayed-onset fetal anomalies. Magnetic resonance imaging (MRI) is particularly useful for diagnosing abnormalities in the fetal nervous system, providing more accurate assessments of ventricular expansion and surrounding brain parenchyma development. MRI is often employed as a follow-up diagnostic tool late in pregnancy when abnormalities are noted on ultrasound.
Management
It is suggested for women of childbearing age to undergo TORCH screening before pregnancy to determine pre-pregnancy infection status. Routine screening for all pregnant women is not recommended. Instead, screening is advised for those with symptoms of infection, close contact with infected individuals, or abnormal fetal findings on ultrasound. Prognostic evaluation and management for fetuses with intrauterine infections require a comprehensive assessment based on the type of maternal pathogen, infection status (primary or reactivation), gestational age and duration of infection, results from invasive prenatal diagnostic tests, and fetal abnormalities detected on ultrasound. A termination of pregnancy should not be recommended solely based on serological testing results.
Toxoplasmosis
For pregnant women with acute infections in early pregnancy, oral spiramycin at a dose of 3 g daily for 7–10 days is used. Although spiramycin crosses the placenta minimally and does not prevent intrauterine infection, it reduces the rate of vertical transmission. For infections occurring after 18 weeks of gestation or when fetal infection is suspected, combination therapy with pyrimethamine, sulfadiazine, and folinic acid is used. Combined therapy is more effective than spiramycin alone in crossing the placenta, eliminating Toxoplasma, and reducing the severity of complications in infected fetuses.
Rubella Virus (RV) and Cytomegalovirus (CMV) Infections
Currently, no effective treatments for RV or CMV intrauterine infections exist. There is insufficient evidence supporting the use of antiviral therapy to improve perinatal outcomes for fetuses with intrauterine infections caused by RV or CMV. Antiviral drugs are not recommended for these cases; instead, fetal prognosis should be carefully assessed.
Prevention
Early testing, diagnosis, and treatment are advocated for susceptible populations.
Women of childbearing age who test negative for rubella antibodies are recommended to receive rubella vaccination before conception. Pregnancy should be planned 1–3 months after vaccination. Vaccination is contraindicated during pregnancy and within one month prior to conception. However, evidence suggests that accidental pregnancy soon after vaccination or vaccination during early pregnancy does not pose significant risks to either the mother or the fetus.