• Clinical science

Congenital TORCH infections

Abstract

Congenital infections are due to pathogens that are transmitted from mother to child during pregnancy (transplacentally) or delivery (peripartum). They can have a substantial negative impact on fetal and neonatal health. The acronym TORCH stands for the causative pathogens: Toxoplasmosis, Others (including syphilis, listeriosis, varicella, parvovirus B19), Rubella, Cytomegalovirus (CMV), and Herpes simplex virus (HSV). TORCH infections can cause spontaneous abortion, premature birth, and intrauterine growth restriction during pregnancy. TORCH infections can cause numerous complex organ abnormalities, including central nervous system (CNS) abnormalities, cardiac defects, vision and hearing loss, as well as skeletal and endocrine abnormalities. Prophylaxis is of great importance during pregnancy. Primary prevention includes vaccination for varicella and rubella (prior to pregnancy), screening for syphilis, and hygiene measures (washing hands, and avoiding certain foods) during pregnancy. Affected children require long-term follow-up to monitor for hearing loss, ophthalmological abnormalities, and developmental delays.

Several other pathogens can also be vertically transmitted during pregnancy and have detrimental effects on the fetus and/or newborn. These include HIV in pregnancy, perinatal hepatitis B, group B streptococcus (GBS), E. coli, gonococcal infection and chlamydial infections, West Nile virus, Zika virus, measles virus, enterovirus, and adenovirus. These conditions are discussed in more detail in their respective learning cards.

Overview

Overview of TORCH infections
Clinical features Diagnosis Treatment
Toxoplasmosis
  • Classic triad
  • Pyrimethamine, sulfadiazine, and folinic acid
Syphilis
Listeriosis
  • Bacterial culture
VZV
Parvovirus B19
Rubella
  • Blueberry muffin appearance (skin lesions that indicate extramedullary hematopoeisis)
  • Congenital rubella syndrome (rare in developed countries):
    • IUGR
    • Sensorineural deafness (DDx CMV!)
    • Cataracts
    • Heart defects (e.g., PDA, pulmonary artery stenosis)
    • CNS abnormalities
    • Hepatitis
  • Supportive care
CMV
  • Jaundice, hepatosplenomegaly
  • IUGR
  • Chorioretinitis
  • Sensorineural deafness
  • Periventricular calcifications
  • Microcephaly
  • Seizures
HSV
  • Premature birth, IUGR
  • Skin, eyes, and mouth (SEM) involvement: vesicular lesions, keratoconjunctivitis
  • Localized CNS involvement: meningitis
  • Disseminated disease: multiple organ involvement, sepsis
  • Viral culture
  • PCR for HSV DNA

Transplacental transmission occurs following primary infection of a seronegative mother during pregnancy → maternal IgM antibodies (which are unable to cross the placenta) form first, and protective IgG antibodies (which are able to cross the placenta) have not yet been formed → the infant is not protected from infection via the placenta!

In general, the earlier the TORCH infection occurs during pregnancy, the more severe the complications.

Attenuated live vaccines (measles, mumps, rubella, and varicella) are contraindicated in pregnancy! Conception should be avoided for at least 3 months after immunization with live vaccines!References: [1][2]

Congenital toxoplasmosis

Onset Characteristic features Sequelae of congenital toxoplasmosis
First trimester
  • Epilepsy
  • Intellectual disability
  • Visual disabilities (chorioretinitis → increased risk of retinal lesions extends into the adult years; cataracts, glaucoma)
Second or third trimester
  • Diagnosis
  • Treatment
    • If a pregnant woman is newly diagnosed with toxoplasmosis: immediately treat with spiramycin
    • If fetal infection is confirmed (or highly suspected): switch to pyrimethamine, sulfadiazine, and folinic acid
    • For newborn infection: also pyrimethamine, sulfadiazine, and folinic acid
  • Prevention
    • Avoid raw, undercooked, and cured meats
    • See food and water safety
    • Frequent hand washing, especially after gardening or touching soil
    • Avoid contact with cat litter

The 4 Cs of congenital toxoplasmosis: Cerebral calcifications, Chorioretinitis, hydroCephalus, Convulsions!
References:[3][4][5][2][6]

Congenital syphilis

  • Epidemiology: ∼ 10:100,000 live births/year
  • Pathogen: Treponema pallidum
  • Transmission
    • Pregnant women: See learning card on syphilis.
    • Fetus: Transplacental transmission from an infected mother
  • Clinical features
Onset Characteristic features

Early congenital syphilis (onset prior to 2 years of age)

  • Hepatomegaly and jaundice
  • Rhinorrhea with white or bloody nasal discharge (“snuffles”)
  • Maculopapular rash on palms and soles
  • Skeletal abnormalities (e.g., metaphyseal dystrophy, periostitis)
  • Generalized lymphadenopathy (nontender)
Late congenital syphilis (onset after 2 years of age)
  • Typical facial features: saddle nose, frontal bossing, short maxilla
  • Dental findings: Hutchinson teeth (notched, widely spaced teeth) and mulberry molars (poorly developed first molars)
  • Eyes and ears: interstitial keratitis, sensorineural hearing loss, and other abnormalities
  • Skin: rhagades (perioral fissures; when fissures heal and leave scars they are referred to as Parrot lines), gummas
  • Skeletal: “saber shins (anterior bowing of the tibia), painless arthritis in knees and other joints
  • Neurological: cranial nerve defects, intellectual disability, hydrocephalus

Hutchinson's triad: interstitial keratitis, sensorineural hearing loss, Hutchinson teeth!

References:[7][8][9][10][11][12][13]

Congenital and newborn listeriosis


References:[14][13][15][16][17][18][19]

Congenital and perinatal varicella infection

  • Epidemiology: Seroprevalence in the general population is ∼ 95% → most mothers already have immunity → rare in newborns
  • Pathogen: varicella-zoster virus (VZV)
  • Transmission
    • Pregnant women: See learning cards on chickenpox and shingles.
    • Fetus
      • Vertical transmission during pregnancy or delivery
      • Postnatally from infected individuals
  • Clinical features
Onset Characteristic features
Congenital varicella syndrome (infection during the first and second trimester)
Neonatal varicella
  • Diagnosis
    • Newborn and pregnant women: usually a clinical diagnosis based on appearance of skin lesions (see the chickenpox and/or shingles learning cards for more details)
      • DFA or PCR of fluid collected from blisters or CSF
      • Serology
    • Fetus: PCR for VZV DNA (in fetal blood, amniotic fluid) and ultrasound to detect fetal abnormalities
  • Treatment
  • Prevention
    • Immunization of seronegative women before pregnancy
    • VZIG in pregnant women without immunity within 10 days of exposure
    • Nationally notifiable condition: Varicella should be reported to the local or state health department.

References:[20][13][21][22]

Congenital parvovirus B19 infection

  • Epidemiology: incidence of acute parvovirus B19 infection in pregnancy ∼ 5% (especially high in daycare workers and elementary school teachers)
  • Pathogen: parvovirus B19
  • Transmission
    • Pregnant women: See the learning card on fifth disease.
    • Fetus: transplacental transmission from infected mother
  • Clinical features
    • Severe anemia and possibility of fetal hydrops
    • Fetal demise and miscarriage or stillbirth in up to 10% of cases (the risk is highest in the first and second trimester)
    • Most intrauterine infections do not result in fetal developmental defects.
  • Diagnosis
    • Seronegative pregnant woman: serologic assays for IgG and IgM against parvovirus B19
      • Positive IgM and negative IgG → very recent infection (refer to specialist), or false positive (repeat testing)
      • Positive IgM and IgG → acute infection (refer to specialist)
      • Positive IgG and negative IgM → maternal immunity (reassurance)
      • Negative IgG and negative IgM → mother has no immunity (counseling)
    • Fetus
      • PCR for parvovirus B19 DNA (amniotic fluid or blood)
      • In suspected hydrops fetalis: doppler ultrasound of fetal vessels (every 7–10 days) → determination of fetal hemoglobin levels via the umbilical vein in cases of suspected anemia according to doppler ultrasound
  • Treatment: : In cases of severe fetal anemia: intrauterine fetal blood transfusion (If thrombocytopenia if present → additional platelet transfusion)
  • Preventing: hand hygiene

References:[23][24][25][26]

Congenital rubella infection

Triad congenital rubella syndrome: CCC = Cataracts, Cochlear defect, Cardiac abnormality
References:[3][27][28][29][30][31][32][33]

Congenital CMV infection

  • Epidemiology: ∼ 1% of live births in the US
  • Pathogen: cytomegalovirus (CMV), a member of the herpesvirus family
  • Transmission
    • Mother: See learning card on cytomegalovirus infection.
    • Fetus: transplacental from an infected mother
    • Newborn: transmission during birth or postnatal transmission via breastmilk from an infected mother
  • Clinical features
    • ∼ 90% with subclinical infection → ∼ 10% of these develop at least some late complications (especially hearing loss)
    • 10% with symptomatic infection at birth∼ 70–80% of these develop late complications
Fetal infection

Sequelae of fetal and newborn infection

Congenital toxoplasmosis may develop similar symptoms to those of congenital CMV infection and is an important differential diagnosis!
References:[34][35][36]

Herpes simplex virus infection in the newborn

  • Epidemiology: incidence is ∼ 1/3,000–10,000 live births
  • Pathogen: primarily herpes simplex virus 2 (HSV-2); in rare cases, HSV-1
  • Transmission
    • Pregnant women: See learning card on herpes simplex virus infections.
    • Fetus: Intrauterine transmission of HSV is rare.
    • Newborn: primary HSV infection in the genital tract of the mother → perinatal transmission during birth (∼ 30% transmission rate if the mother has not yet undergone seroconversion at the time of delivery)
  • Clinical features
Onset Characteristic features
Intrauterine infection (congenital herpes simplex virus infection) (∼ 5% of cases)
  • Fetal demise, preterm birth, very low birth weight
  • Microcephaly, hydrocephalus, and other CNS defects
  • Microphthalmiaeye damage and chorioretinitis
  • Vesicular skin lesions
Perinatal (85% of cases) und postnatal transmission (10% of cases)
  • Skin, eye, and mouth disease (∼ 45%): vesicular skin lesions, keratoconjunctivitis → cataracts and chorioretinitis, vesicular lesions of the oropharynx
  • CNS disease (∼ 30%): meningoencephalitis (e.g., fever or low body temperature, lethargy, irritability, poor feeding, seizures, bulging fontanelle) and possibly vesicular skin lesions
  • Disseminated disease (∼ 25%): clinical findings similar to sepsis with involvement of organs (e.g., liver, CNS, lungs, heart, adrenals, bone marrow and blood, kidneys, GI tract), vesicular skin lesions, which may appear late in the disease course
  • Diagnosis
    • Fetus
      • Ultrasound may show CNS abnormalities
    • Newborn and pregnant women: typically a clinical diagnosis in women
      • Standard: Viral culture of HSV from skin lesions, conjunctiva, oro- or nasopharynx, rectum
      • Alternative: PCR for HSV DNA (CSF, blood)
  • Treatment
  • Prevention

HSV should be considered in infants up to 6 weeks of age with vesicular skin lesions, symptoms of meningitis/encephalitis or sepsis, or persistent fever and negative cultures. A high index of suspicion is warranted in neonatal HSV. Skin, eye, and mouth disease has a good prognosis if detected and treated early!
References:[37][38][39][40]