Congenital cytomegalovirus infection is the infection of a fetus with cytomegalovirus,
or CMV, during intrauterine life. CMV is among the most common infections that cause defects
during fetal development. It is often grouped with other bacteria, parasites, and viruses
that cause similar illnesses in the newborn, known under the acronym TORCH, which includes
Toxoplasma, Other pathogens - usually syphilis; Rubella; Cytomegalovirus, and Herpes simplex
virus.
CMV belongs to the herpesviridae family of viruses. Herpesviruses are double-stranded
DNA viruses which are surrounded by a lipid envelope. CMV is usually transmitted through
contact with blood and other body fluids like breast milk, saliva, genital secretions, and
urine of an infected person; or from transplanted organs.
Congenital CMV infection occurs when a pregnant woman is infected by CMV for the first time
during the pregnancy, or there’s reactivation of an old infection, or reinfection with a
new strain of CMV. The virus in the mother travels through the placenta to the growing
fetus. The exact mechanism by which CMV causes infection and defects in the developing fetus
is still unknown, but it’s thought to be because of two things. First, CMV can be cytopathic,
or cell-damaging, as it replicates within the cells. It breaks down the cytoskeletons
which maintain the cell structure which results in enlarged cells with intranuclear viral
inclusion bodies, giving it the classic “owl's eye” appearance. It is also possible CMV
slows down the process of mitosis, or cell division. Since mitosis helps drive the development
of the fetus, tissue with infected cells might not grow properly. Second, CMV invades the
endothelium of blood vessels, resulting in vasculitis, or inflammation of blood vessels.
Vasculitis can affect placental as well as fetal blood vessels, causing narrowing of
the vessel wall. And, as a result, not enough blood flows to developing organs, causing
abnormalities. Congenital CMV also increases the risk of intrauterine growth restriction,
meaning the fetus does not grow well, or oligohydramnios or polyhydramnios, which is increased or decreased
amniotic fluid.
Most congenital CMV infections are asymptomatic or silent, with only 1 in 10 infected infants
showing symptoms at birth. The most common clinical manifestations include petechiae,
which is tiny purple, red, or brown spots on the skin; jaundice, when the skin, whites
of the eyes and mucous membranes turn yellow; hepatosplenomegaly which is enlarged liver
and spleen; and microcephaly or an abnormally small head size due to an underdeveloped brain.
The hallmark feature of congenital CMV is progressive, permanent sensorineural hearing
loss, or deafness, which can present at birth or develop later in life. Congenital CMV is
also associated with eye abnormalities such as chorioretinitis, or inflammation of the
choroid and retina, strabismus, or muscle imbalance of the eyes, or cortical vision
impairment. CMV also can cause intellectual disability, developmental delays, behavioral
disorders, motor disabilities, and seizures.
The diagnosis of congenital CMV infection can be made prenatally, before birth, or postnatally,
after birth. Prenatal testing includes ultrasonography of the fetus to detect developmental anomalies,
amniocentesis to obtain amniotic fluid for viral culture or CMV PCR, or fetal blood sampling
for CMV PCR or cytomegalovirus-specific IgM antibody measurement. After birth, diagnosis
is confirmed by PCR or viral isolation from urine or saliva samples in newborns obtained
under three weeks of age. A full physical examination of the baby should be done, looking
for skin rashes, enlarged liver and spleen, and microcephaly. In addition, babies with
congenital CMV should be screened for hearing loss at birth, and periodically during childhood
and adolescence. Some hospitals will screen all babies for CMV who fail their newborn
hearing screening, because CMV can cause congenital hearing loss. Other tests done to assess the
extent of the infection may include a liver panel which might show elevated liver transaminases
or elevated bilirubin levels, a full blood count revealing thrombocytopenia, or low platelets.
Neuroimaging of the brain by ultrasonography, unenhanced CT, or MRI, may be done, which
might detect intracranial calcifications, enlarged ventricles, polymicrogyria, lenticulostriate
vasculopathy, or white matter disease.
Treatment is usually reserved for symptomatic infants, and includes antiviral medications
like ganciclovir and valganciclovir, usually given for a total of six months. The antiviral
medication has been shown to reduce the risk of hearing loss progressing and improves head
size growth and developmental milestones early in life. It does not reverse the damage that’s
already occurred. Other supportive measures, such as blood products and platelet transfusions
can be given. As the child grows, functional therapies such as physical therapy, occupational
therapy, and speech/language therapies and vision therapies also may be needed. Children
with hearing loss may be taught sign language, be fitted for hearing aids, or undergo cochlear
implant procedures.
Prevention of congenital CMV by vaccine, like what is routinely done to prevent congenital
rubella, is not currently available. Women who wish to reduce their risk of CMV infection
during pregnancy should reduce or avoid contact with saliva and urine from toddlers and young
children, who often are asymptomatically shedding CMV, and may be a source of infection.
All right, as a quick recap… Congenital CMV infection occurs when a pregnant woman
infected with CMV passes it on to her growing fetus, which results in fetal infection, and
may, but not always, result in birth defects. Fetal defects caused by CMV are thought to
be caused by a combination of cytopathic effect on fetal cells, and blood vessel injury leading
to decreased blood flow to the developing organs. Clinical manifestations include petechiae,
jaundice, hepatosplenomegaly, sensorineural hearing loss, eye abnormalities, microcephaly,
intellectual disability, developmental delays, behavioral disorders, motor disabilities such
as cerebral palsy, and seizures. Treatment in the symptomatic newborn and young infant
involves antiviral medications like ganciclovir and valganciclovir for a total of six months.
Long term treatment involves therapies to improve milestones, mobility, hearing, speech,
and language. A CMV vaccine is not available, but reducing contact with saliva and urine
during pregnancy may be helpful to reduce CMV transmission.