Congenital TORCH infections

Summary
Congenital infections are caused by pathogens 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 of congenital infections: Toxoplasma gondii, others
(including Treponema pallidum, Listeria, varicella zoster virus, and parvovirus B19), rubella
virus, cytomegalovirus(CMV), and herpes simplex virus (HSV). TORCH infections can cause spontaneous
abortion, premature birth, and intrauterine growth restriction (IUGR). These infections can also cause abnormalities
in the CNS, the skeletal and endocrine systems, and the complex organs (e.g., cardiac defects, vision and hearing
loss). Prophylaxis is of great importance during pregnancy. Primary
prevention includes vaccination for varicella and rubella (prior to pregnancy), hygiene measures (washing hands
and avoiding certain foods), and screening for syphilis during pregnancy. Affected infantsrequire regular follow-
ups 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 streptococci, E.
coli, gonococcal infections and chlamydial infections, West Nile virus, Zika virus, measles virus, enterovirus,
and adenovirus. The pathogens are discussed in more detail in their respective articles.
Overview
Description
Congenital TORCH infections are vertically transmitted infections (acquired directly from the mother and
transmitted to the embryo, fetus, or newborn through the placenta or birth canal) that are capable of significantly
influencing fetal and neonatal morbidity and mortality
 Toxoplasmosis
 Others (e.g., syphilis, varicella, parvovirus B19infection, listeriosis)
 Rubella
 Cytomegaly (CMV)
 Herpes simplex virus (HSV) infection

Common findings
 During pregnancy: may cause intrauterine fetal demise and miscarriage
 In neonates
o Hepatosplenomegaly
o Jaundice
o Lethargy
o Growth retardation
o Thrombocytopenia

Overview of congenital TORCH infections

Infection Clinical features Diagnosis Treatment

Toxoplasmosis  Classic triad  T. gondii-specificIgM  Pyrimet

o Chorioretinitis antibodies
Overview of congenital TORCH infections

Infection Clinical features Diagnosis Treatment

o Hydrocephalus

o Diffuse intracranial calcifications

 PCR for T. gondiiDNA
(ring-enhancinglesions)

 Petechiae and purpura (blueberry muffin rash)

 Early congenital syphilis (onset < 2 years)

o Jaundice and hepatosplenomegaly

o Lymphadenopathy

o Nasal discharge (sniffles)

o Maculopapular rash
 VDRL or RPR
o Skeletal abnormalities
Syphilis  Dark-field microscopy  Penicill
 Late congenital syphilis(onset > 2 years)
 PCR
o Frontal bossing, rhagades

o Hutchinson teeth

o Interstitial keratitis

o Sensorineural deafness

o Saber shins

 Spontaneous abortionand premature birth

 Meningitis, sepsis
Listeriosis  Bacterial culture  Ampici
 Vesicular and pustularskin lesions (granulomatosis

infantiseptica)

 IUGR, premature birth

 Chorioretinitis, cataract  Direct fluorescent antigen test

 Varicel
Varicella zoster  Encephalitis (DFA)
 Acyclov
virus (VZV)  Pneumonia  PCR for VZVDNA
 Breastfe
 CNS abnormalities  Serology (IgM antibodies)

 Hypoplastic limbs

 PCR for parvovirus B19DNA

 Aplastic anemia
Parvovirus B19  Serial ultrasounds to rule  Intraute
 Fetal hydrops
out fetal hydrops
Overview of congenital TORCH infections

Infection Clinical features Diagnosis Treatment

 IUGR

 Sensorineural deafness

 Cataracts  Serology (IgM antibodies)

Rubella  Support
 Heart defects (e.g., PDA, pulmonary arterystenosis)  PCR for rubellaRNA

 CNS abnormalities

 Petechiae and purpura(blueberry muffin rash)

 Jaundice, hepatosplenomegaly

 IUGR

 Chorioretinitis

 Sensorineural deafness  Viral culture  Gancicl

Cytomegalovirus(CMV)
 Periventricular calcifications  PCR for CMVDNA  Support

 Petechiae and purpura(blueberry muffin rash)

 Microcephaly

 Seizures

 Premature birth, IUGR

 Skin, eyes, and mouth involvement: vesicular

Herpes simplex  Viral culture  Acyclov
lesions, keratoconjunctivitis
virus (HSV)  PCR for HSVDNA  Support
 Localized CNSinvolvement: meningoencephalitis

 Multiple organ involvement, sepsis

Transplacental transmission occurs following primary infection of a seronegative mother during pregnancy. Maternal IgM
antibodies, which are unable to cross the placenta, form first. Protective IgG antibodies, which are able to cross the placenta,
have not yet been formed, so the infant is not protected from infection via the placenta.

In general, the earlier in pregnancy a TORCH infection occurs, the more severe the complications.
Attenuated live vaccines (measles, mumps, rubella, and varicella) are contraindicated
in pregnancy.Conception should be avoided for 1 month after immunization with live vaccines.

Congenital toxoplasmosis
Epidemiology
∼ 0.5–1:10,000 live births per year in the US [2]

Pathogen
Toxoplasma gondii
Life cycle of Toxoplasma gondii

The life cycle of toxoplasmosis involves transmission to a human host through the ingestion of cat feces particulate that contains
oocysts or ingestion of meat (i.e., pork) containing Toxoplasma cysts. Cross-placental transmission is possible after the initial
infection of pregnant women.

Transmission
 Mother
o Cat feces
o Raw or insufficiently cooked meat
o Unpasteurized milk (especially goat milk)
o See “Etiology” in “Toxoplasmosis.”
 Fetus
o Transplacental transmission
 First trimester: ∼ 15%
 Third trimester: ∼ 70%

Clinical features [3]

 First trimester
o Increased risk of premature birth and spontaneous abortion
o Classic triad of toxoplasmosis
Chorioretinitis (a form of posterior uveitis)
 Diffuse intracranial calcifications
 Hydrocephalus
o Possible other nonspecific clinical features
 Petechiae and purpura (blueberry muffin rash)
 Fever
 Jaundice
 Hepatosplenomegaly

 Lymphadenopathy
 Pneumonitis
 Seizures
 Macrocephaly or microcephaly [4]

 Thrombocytopenia
 Second or third trimester: subclinical or mild toxoplasmosis
 Sequelae of congenital toxoplasmosis
o Epilepsy
o Intellectual disability
o Visual disabilities (chorioretinitis →increased risk of chorioretinal scars , cataracts,
and glaucoma)
o Sensorineural hearing loss

Blueberry muffin syndrome

Newborn with acute myeloid leukemia (AML)

Multiple bluish-purple macules and nodules are distributed across the face and scalp, with a few extending onto the torso. Jaundice is
also present.

This appearance is termed “blueberry muffin syndrome.” Differential diagnoses include hematological disorders, other malignancies,
and congenital infections (the jaundice in this case may be related to the underlying AML but is not part of the blueberry muffin
appearance itself).
Diagnostics [5]

 Mother: See “Diagnostics” in “Toxoplasmosis.”

 Fetus: PCR for T. gondii DNA in amniotic fluid
 Newborn
o CT/MRI: intracranial calcifications, hydrocephalus, ring-enhancing lesions
o T. gondii-specific IgM antibodies (CSF, serum)
o PCR forT. gondii DNA (CSF, serum)
o Ophthalmological evaluation: chorioretinitis

Congenital toxoplasmosis

Cranial CT scan of an infant (IV contrast; axial view)

The left lateral ventricle is highly dilated (hatched red overlay). Hyperdensities are visible in the parenchyma of the right frontal lobe
(green overlay) and in the occipital lobe (green overlay; white arrow), indicating parenchymal calcifications.
Hydrocephalus (ventriculomegaly) and parenchymal calcifications are typical radiological features of congenital toxoplasmosis.

Internal capsule lesion in neurotoxoplasmosis

MRI head (T2-weighted; with contrast; axial plane) of a patient with cerebral toxoplasmosis

A small nodule (hatched overlay) in the right internal capsule is accompanied by hyperintense perilesional edema (solid overlay).

Neurotoxoplasmosis more commonly manifests with multiple lesions and it has a propensity for the corticomedullary junction,
thalami, and basal ganglia. It is a leading cerebral opportunistic infection in patients with AIDS.

Macular scar in congenital toxoplasmosis

Fundus photography of the left eye of an infant (optic disc not shown)
The macular area shows a sharply demarcated scar with depigmentation and hyperpigmentation, affecting both the retina and
choroid. This clinical finding is a typical sign of congenital toxoplasmosis.

Treatment [5]

 Mother: immediate administration of spiramycin to prevent fetal toxoplasmosis [6]

 Fetus: When confirmed or highly suspected, switch to pyrimethamine, sulfadiazine, and folinic acid.
 Newborn: pyrimethamine, sulfadiazine, and folinic acid

Prevention [3]

 Avoidraw, undercooked, and cured meats.

 Wash hands frequently, especially after touching soil (e.g., during gardening).
 Avoid contact with cat litter.
The 4 Cs of congenital toxoplasmosis: Cerebral calcifications, Chorioretinitis, hydroCephalus, and Convulsions.

Congenital syphilis
Epidemiology
∼ 23:100,000 live births per year in the US [7]

Pathogen
Treponema pallidum

Transmission [7]

 Mother
o Sexual contact (contact with infectious lesion)
o See “Etiology” in “Syphilis.”
 Fetus: transplacental transmission from infected mother
o Increased risk of transmission with recent syphilis infection
o Risk of transmission increases with gestational age
 Neonate: perinatal transmission during birth

Clinical features [8]

 In utero syphilis
o Miscarriage
o Stillbirth
o Hydrops fetalis
 Early congenital syphilis (onset < 2 years of age)
o Hepatomegaly and jaundice
o Rhinorrhea with white or bloody nasal discharge (also called “snuffles”)
o Maculopapular rash on palms and soles; a bullous form of the rash called pemphigus
syphiliticus may be present at birth.
o Skeletal abnormalities (e.g., metaphyseal dystrophy, periostitis)
 o Generalized lymphadenopathy (nontender)
 Late congenital syphilis (onset > 2 years of age)
o Typical facial features: saddle nose, frontal bossing, short maxilla
o Dental findings: Hutchinson's teeth(notched, widely spaced teeth); mulberry molars (poorly
developed first molars)
o Eyes and ears [9]

Syphilitic keratitis: nonulcerative, interstitial keratitis that develops as a late


complication of syphilis
 More common in patients with congenital syphilis than acquired syphilis
 Causes stromal inflammation
 Sensorineural hearing loss
o Skin: rhagades (perioral fissures, cracks, and/or scars, particularly near the corners of the mouth
and nose)
o Skeletal
Saber shins

 An anterior bowing of the tibia, causing it to resemble a saber
 Other causes include rickets and Paget disease of bone.
 Painless arthritis in knees and other joints
o Neurological: cranial nerve palsies (e.g., CN VIII defect causing deafness), intellectual
disability, hydrocephalus
Congenital syphilis
Epidemiology
∼ 23:100,000 live births per year in the US [7]

Pathogen
Treponema pallidum

Transmission [7]

 Mother
o Sexual contact (contact with infectious lesion)
o See “Etiology” in “Syphilis.”
 Fetus: transplacental transmission from infected mother
o Increased risk of transmission with recent syphilis infection
o Risk of transmission increases with gestational age
 Neonate: perinatal transmission during birth

Clinical features [8]

 In utero syphilis
o Miscarriage
o Stillbirth
o Hydrops fetalis
 Early congenital syphilis (onset < 2 years of age)
o Hepatomegaly and jaundice
o Rhinorrhea with white or bloody nasal discharge (also called “snuffles”)
 o Maculopapular rash on palms and soles; a bullous form of the rash called pemphigus
syphiliticus may be present at birth.
o Skeletal abnormalities (e.g., metaphyseal dystrophy, periostitis)
o Generalized lymphadenopathy (nontender)
 Late congenital syphilis (onset > 2 years of age)
o Typical facial features: saddle nose, frontal bossing, short maxilla
o Dental findings: Hutchinson's teeth(notched, widely spaced teeth); mulberry molars (poorly
developed first molars)
o Eyes and ears [9]

 Syphilitic keratitis: nonulcerative, interstitial keratitis that develops as a late

complication of syphilis
 More common in patients with congenital syphilis than acquired syphilis
 Causes stromal inflammation
 Sensorineural hearing loss
o Skin: rhagades (perioral fissures, cracks, and/or scars, particularly near the corners of the mouth
and nose)
o Skeletal
 Saber shins
 An anterior bowing of the tibia, causing it to resemble a saber
 Other causes include rickets and Paget disease of bone.
 Painless arthritis in knees and other joints
o Neurological: cranial nerve palsies (e.g., CN VIII defect causing deafness), intellectual
disability, hydrocephalus

Skin alterations in congenital syphilis

Plantar surfaces of the feet in a newborn with congenital syphilis

The right foot shows a fluid-filled blister. The left foot shows a blister that has already peeled.

These features suggest pemphigus syphiliticus, which is pathognomonic for congenital syphilis.

Hutchinson's Teeth resulting from congenital syphilis

The central incisor teeth are narrow and notched (Hutchinson teeth), while the molars are not fully developed (mulberry molars).
These findings occur after continued inflammation and scar formation through congenital syphilis.
Newborn with congenital syphilis

A face of a newborn infant with perioral fissures (rhagades; indicated by black arrow) and nasal discharge (indicated by white arrow)
can be seen.

These clinical features are characteristic of congenital syphilis.

Diagnosis [10]

 Newborn and mother

o Initial test: RPR or VDRL (serum)
o Confirmatory test: dark-field microscopy or PCR of lesions or bodily fluids
o See “Diagnostics” in syphilis.
 Fetus: repeated ultrasound examinations (placentomegaly, hepatomegaly, ascites, and/or hydrops fetalis)

Spirochetes on dark-field microscopy

Photomicrograph of rabbit testicular tissue (dark-field microscopy combined with immunofluorescence; 54x magnification)

Spiral bacteria are visible, which is the characteristic appearance of spirochetes.

Treatment
 10 days of IV penicillin G for both pregnant women and newborns [10]

 See “Treatment” in “Syphilis.”

Prevention [7]
  Maternal screening and, if positive, antibiotictreatment: should take place in
early pregnancy because placental transmission is most likely to occur after the first trimester.
 Nationally notifiable condition: Congenital syphilis and syphilitic childbirth must be reported to the local or
state health department.
Hutchinson triad: interstitial keratitis, sensorineural hearing loss, Hutchinson teeth

Congenital listeriosis
Epidemiology
∼ 3:100,000 live births per year in the US [11]

Pathogen
Listeria monocytogenes

Transmission [12]

 Mother
o Contaminated food: especially raw milk products
o Other possible sources: fish, meat, and industrially processed vegetables (e.g., ready-
made salads)
o See “Etiology” in “Listeriosis.”
 Fetus
o Transplacental transmission from an infected mother
o Direct contact with infected vaginal secretions and/or blood during delivery

Clinical features [13]

 Listeriosisof pregnancy
o Increased risk of premature birth and spontaneous abortion
o Early-onset syndrome: granulomatosis infantiseptica
 Severe systemic infection characterized by disseminated abscesses (may develop in
any organ system)
 Most common findings: respiratory distress and skin lesions
 Signs of meningitis may already develop.
 Neonatal listeriosis
o Late-onset syndrome (5 days to 3 weeksafter birth): Listeria meningitis/encephalitis
o See “Neonatal infection.”

Diagnosis
Culture from blood or CSF samples (pleocytosis) [14]

Treatment
IV ampicillin and gentamicin (for both mother and newborn) [14]

Prevention [12]

 Avoidance of soft cheeses

 Avoidance of potentially contaminated water and food
  Nationallynotifiable condition: Listeriosismust be reported to the local or state health department.
 See “Food and water safety.”

Congenital varicella infection

Epidemiology
 Seroprevalence in the general population is ∼ 95%. [15]

 Most mothers have been vaccinated, so congenital infection is rare (< 2%). [15]

Pathogen
Varicella-zoster virus (VZV)

Transmission [16]

 Mother
o Primary infection
Airborne droplets

 Direct skin contact with vesicle fluid
o Reactivation: usually in immunocompromised individuals
o See “Chickenpox” and “Shingles.”
 Fetus: transplacental transmission from an infected mother

Clinical features [16]

 Congenital varicella syndrome (infection during first and second trimester) [17]

o Hypertrophic scars (cicatricial skin lesions)

o Limb defects (e.g., hypoplasia)
o Ocular defects (e.g., chorioretinitis, cataracts, microphthalmia)
o CNS defects (e.g., cortical atrophy, seizures, intellectual disability), hydrocephalus
 Neonatal varicella
o Mild infection (maternal exanthem > 5 daysbefore birth)
o Severe infection (maternal exanthem< 5 days before birth):
hemorrhagic exanthem, encephalitis, pneumonia, or congenital varicella syndrome (mortality
rate of up to 30%)

Diagnosis [16]

 Newborn and mother

o Usually clinical diagnosis is confirmed by appearance of skin lesions
o DFA or PCR of fluid collected from blistersor cerebrospinal fluid (CSF)
o Serology
 Fetus: PCR for VZV DNA (in fetal blood, amniotic fluid) and ultrasound to detect fetal abnormalities

Treatment [16]

 For pregnant women or newborns with (severe) infection: acyclovir

 Administer postexposure prophylaxis in newborns if mother displays symptoms of varicella < 5 days before
delivery: IgG antibodies (varicella-zoster immune globulin, VZIG) [18]

 For other indications for varicellapostexposure prophylaxis, see “Prevention” in “Varicella.”

  Cesarean delivery if lesions are present at the delivery
 Breastfeeding is encouraged because of the possible protective effect of antibodies in breast milk.

Prevention
 Immunization of seronegative women before pregnancy
 VZIG in pregnant women without immunitywithin 10 days of exposure
 Nationally notifiable condition: Varicella must be reported to the local or state health department.


Parvovirus B19
 Mechanism of action: infection of erythrocyteprogenitor cells in bone marrow and endothelial cells by
attaching to their P antigen → cell destruction → hydrops fetalisin neonates and pure RBC aplasia in
adults

Transmission
 Mother
o Mainly via aerosols
o Rarely hematogenous transmission
o See “Fifth disease.”
 Fetus: transplacental transmission from infected mother

Clinical features [19]

 Severe anemia and possibly fetal hydrops

 Fetal demise and miscarriage/stillbirth in approximately 10% of cases (Risk is highest in the first and
second trimesters.)
 Most intrauterine infections do not result in fetal developmental defects.

Diagnosis
 Mother: serologic assays for IgG and IgMagainst parvovirus B19

Serologic assay analysis for parvovirus B19

Results Positive IgM Negative IgM

Positive I  Acute  Maternal im

gG
inf munity

ect  Reassurance

ion

 Refer

to

sp

eci

ali
 Serologic assay analysis for parvovirus B19

Results Positive IgM Negative IgM

st

 Very

rec

ent

inf

ect  No

Negative ion maternal i

IgG  Refer mmunity

to  Counseling

sp

eci

ali

st

 Fetus [19]

o PCR for parvovirus B19 DNA (amniotic fluidor blood)

o Periodic ultrasound of fetal vessels for anemia and hydrops fetalis (every 1–2 weeks)
o In cases of suspected anemia according to Doppler ultrasound, fetal hemoglobin levels are
determined via the umbilical vein.

Treatment
 Intrauterinefetal blood transfusion in cases of severe fetal anemia
 Additional platelet transfusion if thrombocytopenia is also present

Prevention
 Hand hygiene (frequent hand washing)
 Pregnant women with risk factors for TORCH infection should avoid potentially contaminated workplaces
(e.g., schools, pediatric clinics).

Congenital rubella infection

Epidemiology
Most mothers have been vaccinated, so congenital infection is very rare. [20]

Pathogen
Rubella virus

Transmission
  Mother
o Mainly via airborne droplets
o See “Rubella.”
 Fetus
o Transplacental from infected mother
o Risk of fetal infection is high in the first trimester, decreased in the second trimesterand then
increased again in the third trimester. [21]

o Risk of congenital rubella syndrome [22]

 1–12 weeks gestation (period of organogenesis): highest risk

 12–20 weeks gestation: very low
 > 20 weeks gestation: no documented cases

Clinical features [22]

 Intrauterine rubella infection: miscarriage, preterm birth, fetal growth restriction(especially likely if
infection occurs during the first trimester)
 Congenital rubella syndrome
o Triad of congenital rubella syndrome
Cardiac defect: most common defect (e.g., patent ductus arteriosus, pulmonary
artery stenosis)
 Cataracts: Other eye manifestations may also occur later in life,
including glaucomaand salt and pepper retinopathy(abnormal retinal pigmentation)
 Cochlear defect: bilateral sensorineural hearing loss
o Early features
Hepatosplenomegaly, jaundice
 Hemolytic anemia, thrombocytopenia
 Petechiae and purpura, i.e., blueberry muffin rash (due to extramedullary
hematopoiesis in the skin)
 Transient meningitis and/or encephalitis
 Pneumonia
o Late features
 CNS defects: microcephaly, intellectual disability, panencephalitis
 Skeletal abnormalities
 Endocrine disorders (e.g., diabetes, thyroid dysfunction)
 Vascular disease
 Immune defects
Morgagnian (hypermature) cataract

Slit-lamp photography

The completely opacified lens is visible in the pupil. Its darker, inferior part represents the sunken nucleus (blue overlay) within the
liquified cortex (white upper part; yellow overlay). This is the typical appearance of Morgagnian hypermature cataract. The anterior
chamber shows deposits, probably macrophages filled with lens protein (examples indicated by arrowheads). This suggests a
phacocytic process, which, if left untreated, can lead to phacolytic glaucoma.

Hatched overlay: optical cross-section of the cornea; produced by slit-lamp

Diagnosis [23]

 Newborn and mother

o PCR for rubella RNA (throat swab, CSF)
o Serology (abnormally high or persistent concentrations of IgM and/or IgG antibodies)
o Viral culture (nasopharynx, blood)
 Fetus
o IgM antibody serology (chorionic villi, amniotic fluid)
o PCR for rubella RNA (chorionic villi, amniotic fluid)

Treatment
 Intrauterine rubella infection [23]

o < 16 weeks: Counsel about potential maternal-fetal transmission and the possibility of
terminating the pregnancy.
o > 16 weeks: reassurance and symptomatic therapy (e.g., acetaminophen)
  Congenital rubella syndrome: supportive care (based on individual disease manifestations) and
surveillance (including monitoring for late-term complications)

Prevention [24]

 Immunization of seronegative women before pregnancy

 Nationally notifiable condition: Suspected congenital rubella syndrome must be reported to the local or state
health department.
CCC-Triad of congenital rubella syndrome: Cataracts, Cochlear defects, Cardiac abnormality

Congenital CMV infection

Epidemiology
∼ 0.5–1% of live births per year in the US [25]

Pathogen
Cytomegalovirus

Transmission
 Mother: via CMV-contaminated blood, urine, saliva, and genital secretions
o Blood transfusions
o Sexual transmission
o Droplet transmission
o Transplant-transmitted infection (e.g., bone marrow, lungs, kidneys)
o See “Cytomegalovirus infection.”
 Fetus:
transplacental transmission from an infected mother
 Newborn: during birth or postnatal via breastmilk from infected mother

Clinical features [26]

 Fetal infection
o Increased risk of fetal demise
o IUGR
o Oligohydramnios or polyhydramnios, placental abnormalities
 Newborn infection
o Severity
 Subclinical infection (∼ 90%): ∼ 10% go on to develop a late complication (most
commonly hearing loss) [26]

 Symptomatic infection at birth (∼ 10%): ∼ 70–80% go on to develop a late

complication.
o CNS findings
Hydrocephalus

 Microcephaly .
o Sensorineural hearing loss (∼ 30%) [27]

o Chorioretinitis (∼ 10%)
o Nonspecific findings (similar to other TORCH infections)
 Petechiae, purpura (blueberry muffin rash)
  Hepatosplenomegaly, jaundice
 Small for gestational age (SGA)
 Seizures, lethargy, poor suck
 Hemolytic anemia, thrombocytopenia
 Pneumonia
o Late complications
 Hearing loss, vision impairment
 Psychomotor retardation, intellectual disability
 Dental abnormalities

Diagnosis [28][29]

 Fetus and newborn

o CNS imaging: hydrocephalus, periventricular calcifications, or intraventricular hemorrhage
o Ultrasound: periventricular calcifications, hyperechogenic foci (bowel and liver, ascites),
and hydrops fetalis
 Newborn and mother
o CMV IgM antibodies (blood)
o Viral culture or PCR for CMV DNA (urine, saliva)
 Fetus
o Viral culture or PCR for CMV DNA(amniotic fluid)
o CMV IgM antibodies (fetal blood)

Congenital CMV infection

Ultrasound of the CNS, parasagittal section: dilated lateral ventricles with hyperechoic deposits that are compatible with
intraventricular hemorrhage

Congenital CMV infection

Ultrasound of the CNS, coronal section: dilated lateral ventricles with hyperechoic deposits that are compatible with intraventricular
hemorrhage (green areas). (Arrow = periventricular calcification)

Differential diagnosis [28]

 Congenital toxoplasmosis
o Causes chorioretinitis, hydrocephalus, and intracranial calcifications
o Intracranial calcifications in congenital toxoplasmosis typically show ring-enhancement.

Treatment
 Fetus
o Severe anemia: intrauterine blood transfusions
o Thrombocytopenia: platelet transfusions
 Newborn
o Supportive therapy of symptoms (e.g., fluid
and electrolyte imbalances, anemia, thrombocytopenia, seizures, secondary infections)
o Ganciclovir, valganciclovir, or foscarnet
 Mother: valacyclovir is the only therapy approved during pregnancy [30]

Prevention
  Frequenthand washing, especially after contact with bodily secretions of small children (e.g., diaper
changing)
 Avoidance of food sharing with children
 Avoidance of kissing small children on the mouth
Congenital toxoplasmosis may manifest with symptoms resembling congenital CMV infection.

Congenital herpes simplex virus infection

Epidemiology
∼ 1:3,000–10,000 live births per year [31]

Pathogen
Mainly herpes simplex virus 2 (HSV-2); in rare cases HSV-1

Transmission [31]

 Mother
o Primary infection: contact with contaminated oral secretions via small skinlesions
o Reactivation: usually in immunocompromised individuals
o See “Herpes simplex virus infections.”
 Fetus:
transplacental transmission from an infected mother (rare)
 Newborn: perinatal transmission during birth(∼ 30% transmission rate if mother has not yet
undergone seroconversion at time of delivery)

Clinical features [32]

 Intrauterine HSV infection (∼ 5% of cases)

o Fetal demise, preterm birth, very low birth weight
o Microcephaly, hydrocephalus, and other CNS defects
o Microphthalmia and chorioretinitis
o Vesicular skin lesions
 Perinatal and postnatal transmission
o Skin, eye, and mouth disease
Vesicular skin lesions

 Keratoconjunctivitis leading to cataracts, chorioretinitis
 Vesicular lesions of oropharynx
o CNS disease
Meningoencephalitis (manifesting with fever, lethargy, irritability, poor

feeding, seizures, bulging fontanelle)
 Possibly vesicular skin lesions
o Disseminated disease
 Features similar to those of sepsis, with organ involvement
(e.g., liver, CNS, lungs, heart, adrenal glands, kidneys, GI tract)
 Vesicular skin lesions (may not appear until late in disease course)

Diagnosis
  Mother: typically a clinical diagnosis
 Fetus: The ultrasound may show CNSabnormalities.
 Newborn: Perform neonatal HSV testing.
o Standard: viral culture of HSV from skinlesions, conjunctiva, oro/nasopharynx, or rectum
o Alternative: PCR for HSV DNA (CSF, blood)

Treatment [33]

 Newborn and mother: IV acyclovir or valacyclovir

 Additionally in newborns: supportive therapy of fluid/electrolyte imbalances, SIRS, septic shock, seizures,
secondary infections, etc.

Prevention
 Antiviral therapy (acyclovir) beginning at 36 weeks of gestation for individuals with a known history
of HSV lesions
 Cesarean delivery in women with active genital lesions or prodromal symptoms (e.g., burning pain)
HSV should be considered in infantsup to 6 weeks of age with vesicular skin lesions, persistent fever with negative
cultures, and/or symptoms of meningitis, encephalitis or sepsis.
Skin, eye, and mouth disease caused by HSV has a good prognosis if detected and treated early.

References
1.Andreas Sauerbrei, MD. Preventing congenital varicella syndrome with immunization. Canadian Medical
Association Journal. 2011.
2.Peyron F, Mc Leod R, Ajzenberg D, et al. Congenital Toxoplasmosis in France and the United States: One
Parasite, Two Diverging Approaches. PLoS Negl Trop Dis. 2017; 11(2):
p.e0005222. doi: 10.1371/journal.pntd.0005222.
3.McAuley JB. Congenital Toxoplasmosis. Journal of the Pediatric Infectious Diseases Society. 2014; 3(suppl_1):
p.S30-S35. doi: 10.1093/jpids/piu077.
4.Patel P. Congenital Infections of the Nervous System. CONTINUUM: Lifelong Learning in Neurology. 2021;
27(4): p.1105-1126. doi: 10.1212/con.0000000000000991.
5.McLeod R, Boyer K, Karrison T, et al. Outcome of Treatment for Congenital Toxoplasmosis, 1981-2004: The
National Collaborative Chicago-Based, Congenital Toxoplasmosis Study. Clinical Infectious Diseases. 2006;
42(10): p.1383-1394. doi: 10.1086/501360.
6.Toxoplasmosis in Pregnancy. https://www.glowm.com/section_view/heading/Toxoplasmosis%20in
%20Pregnancy/item/187. Accessed: May 31, 2019.
7.Sexually Transmitted Disease Surveillance 2017. https://www.cdc.gov/std/stats17/Syphilis.htm. Updated: July 24,
2018. Accessed: October 25, 2020.
8.Lago EG, Vaccari A, Fiori RM. Clinical Features and Follow-up of Congenital Syphilis. Sex Transm Dis. 2013;
40(2): p.85-94. doi: 10.1097/olq.0b013e31827bd688.
9.L. Pessoa, V. Galvao. Clinical aspects of congenital syphilis with Hutchinson's triad. Case Reports. 2011;
2011(dec21 1): p.bcr1120115130-bcr1120115130. doi: 10.1136/bcr.11.2011.5130.|
10.Wendel Jr. GD, Sheffield JS, Hollier LM, Hill JB, Ramsey PS, Sánchez PJ. Treatment of Syphilis in Pregnancy
and Prevention of Congenital Syphilis. Clinical Infectious Diseases. 2002; 35(s2): p.S200-
S209. doi: 10.1086/342108.
11.2017 Nationally Notifiable Conditions. https://wwwn.cdc.gov/nndss/conditions/notifiable/2017/. Updated:
January 1, 2017. Accessed: March 22, 2017.
12.Janakiraman V. Listeriosis in pregnancy: diagnosis, treatment, and prevention. Rev Obstet Gynecol. 2008; 1(4):
p.179-85. pmid: 19173022. |
13.Mardis BA, Conley CS, Kyle JA. Listeriosis: An Overview. US Pharm. 2012; 37(8): p.38-41.
14.Madjunkov M, Chaudhry S, Ito S. Listeriosis during pregnancy. Arch Gynecol Obstet. 2017; 296(2): p.143-
152. doi: 10.1007/s00404-017-4401-1.
15.Varicella. https://www.cdc.gov/vaccines/pubs/pinkbook/varicella.html. Updated: April 15, 2019. Accessed:
October 25, 2020.
16.Smith CK, Arvin AM. Varicella in the fetus and newborn. Seminars in Fetal and Neonatal Medicine. 2009;
14(4): p.209-217. doi: 10.1016/j.siny.2008.11.008.|
17.Auriti C, Piersigilli F, De Gasperis MR, Seganti G. Congenital Varicella Syndrome: Still a Problem?. Fetal
Diagn Ther. 2009; 25(2): p.224-229. doi: 10.1159/000220602.
18.Shrim A, Koren G, Yudin MH, et al. Management of Varicella Infection (Chickenpox) in Pregnancy. Journal of
Obstetrics and Gynaecology Canada. 2012; 34(3): p.287-292. doi: 10.1016/s1701-2163(16)35190-8.
19.Lamont RF, Sobel JD, Vaisbuch E, et al. Parvovirus B19 infection in human pregnancy. BJOG. 2010; 118(2):
p.175-186.doi: 10.1111/j.1471-0528.2010.02749.x.
20.Centers for Disease Control and Prevention. Three Cases of Congenital Rubella Syndrome in the Postelimination
Era: Maryland, Alabama, and Illinois, 2012. MMWR Morb Mortal Wkly Rep. 2013; 62(12): p.226-229.
21.Katow S. Rubella Virus Genome Diagnosis during Pregnancy and Mechanism of Congenital
Rubella. Intervirology. 1998; 41(4-5): p.163-169. doi: 10.1159/000024931.
22.Chapter 15: Congenital Rubella Syndrome. https://www.cdc.gov/vaccines/pubs/surv-manual/chpt15-
crs.html. Updated: April 28, 2020. Accessed: October 26, 2020.
23.Dontigny L, Arsenault MY, Martel MJ, et al. SOGC Clinical Practice Guidelines: Rubella in Pregnancy. J
Obstet Gynaecol Can. 2008; 30(2): p.152–158. doi: 10.1016/S1701-2163(16)32740-2.|
24.Prevention of Measles, Rubella, Congenital Rubella Syndrome, and Mumps, 2013: Summary Recommendations
of the Advisory Committee on Immunization Practices (ACIP).. https://www.jstor.org/stable/24832555?
seq=1. Updated: June 14, 2013. Accessed: October 26, 2020.
25.Congenital CMV Infection. https://www.cdc.gov/cmv/clinical/congenital-cmv.html. Updated: April 28,
2020. Accessed: October 26, 2020.
26.Boppana SB, Ross SA, Fowler KB. Congenital Cytomegalovirus Infection: Clinical Outcome. Clinical
Infectious Diseases. 2013; 57(suppl 4): p.S178-S181. doi: 10.1093/cid/cit629.|
27.Fowler KB, Boppana SB. Congenital cytomegalovirus (CMV) infection and hearing deficit. Journal of Clinical
Virology. 2006; 35(2): p.226-231. doi: 10.1016/j.jcv.2005.09.016.|
28.Kathleen R. Fink, MD, Mahesh M. Thapa, MD, Gisele E. Ishak, MD Sumit Pruthi, MD. Neuroimaging of
Pediatric Central Nervous System Cytomegalovirus Infection. Radiological Society of North America. 2010.
29.Lipitz S, Yinon Y, Malinger G, et al. Risk of cytomegalovirus-associated sequelae in relation to time of infection
and findings on prenatal imaging. Ultrasound Obstet Gynecol. 2013; 41(5): p.508-514. doi: 10.1002/uog.12377.|
30.Khalil, A, Heath P, Jones, C, Soe A, Ville YG on behalf of the Royal College of Obstetricians and
Gynecologists. Congenital Cytomegalovirus Infection: Update on Treatment. BJOG: An International Journal of
Obstetrics & Gynaecology. 2017; 125(1): p.e1-e11. doi: 10.1111/1471-0528.14836.|
31.Xu F, Sternberg MR, Kottiri BJ, et al. Trends in Herpes Simplex Virus Type 1 and Type 2 Seroprevalence in the
United States. JAMA. 2006; 296(8): p.964. doi: 10.1001/jama.296.8.964.|
32.Rudnick CM, Hoekzema GS. Neonatal Herpes Simplex Virus Infections. Am Fam Physician. 2002; 65(6):
p.1138-1142.
33.James SH, Kimberlin DW. Neonatal Herpes Simplex Virus Infection. Clin Perinatol. 2015; 42(1): p.47-
59. doi: 10.1016/j.clp.2014.10.005