Congenital CMV

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Dima Nimri, M.D. [2]

Overview

Congenital CMV infection is the most common congenital infection worldwide. Its incidence ranges between 0.4% to 2.0% worldwide. The infection can be asymptomatic at birth, or can have severe symptoms such as microcephaly, SGA and hypotonia. One of the most common complications of congenital CMV infection is sensorineural hearing loss. There is no universal screening for pregnant women for CMV infection. Congenital CMV infection must be differentiated from other congenital infections (TORCH infections). The diagnosis is made by the typical findings on a prenatal ultrasound, along with isolation of the virus from fetal tissue. Treatment with antiviral medications improves auditory sequelae in these infants, but not the neurological outcome.

Historical Perspective

  • In 1947, congenital CMV infection was described as inclusion disease of infancy.[1]
  • In 1960, the term cytomegalovirus was proposed.[2]
  • In 1971, prenatal diagnosis of congenital CMV was first reported by isolating CMV from amniotic fluid.[3]

Classification

Congenital CMV infection can be classified based on the initial presentation at birth:

  • Asymptomatic congenital CMV infection
  • Symptomatic congenital CMV infection

Pathophysiology

Pathogenesis

The pathogenesis of congenital CMV infection is largely unknown and poorly understood. However, the clinical manifestations are thought to arise as a result of direct injury to the fetal cells from CMV virus or due to decreased function of the placenta as a result of the infection.[4]

Microscopic Pathology

Microscopic pathology of CMV placentitis on H&E staining showing CMV-infected cells - By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=7350260

Causes

The cause of congenital CMV is cytomegalovirus. For more information about the causative agent, click here.

Differentiating Congenital CMV from Other Congenital Infections

The most important congenital infections, which can be transmitted vertically from mother to fetus are the TORCH infections. These infections have overlapping features and hence, must be differentiated from congenital CMV infection:[5]

Congenital Infection Cardiac Findings Skin Findings Ocular Findings Hepatosplenomegaly Hydrocephaly Microcephaly Intracranial Calcifications Hearing deficits
Cytomegalovirus (CMV) Periventricular calcifications
Toxoplasmosis Diffuse intracranial calcifications
Treponema pallidum
Rubella
Herpes simplex virus (HSV)
Parvovirus B19

Epidemiology and Demographics

Epidemiology

Incidence

The worldwide incidence of congenital CMV infection ranges between 400 to 2,000 per 100,000 cases.[6][7][8][9][10][11][10][12][13][14]

Demographics

Race

Congenital CMV infection is more common among non-whites.[10]

Socioeconomic Status

Congenital CMV infection is more common among low socioeconomic status.[10]

Risk Factors

Risk factors to congenital CMV infection include:[10]

Screening

There are no screening recommendations for congenital CMV.[20]

Natural History, Complications and Prognosis

Natural History

Treatment of congenital CMV infection can only improve hearing outcomes. Depending of the initial presentation at birth and severity of symptoms, the natural history of the disease can have severe and debilitating long-term complications.

Complications

Common Complications

Common complications in infants with congenital CMV infection include:[21]

Less Common Complications

Less common complications of congenital CMV infection include:[21]

Prognosis

The prognosis of congenital CMV infection is usually poor with development of long-term complications, such as hearing loss and developmental delay.

History and Symptoms

Symptoms in the Mother

Mothers with primary or recurrent CMV infection are usually asymptomatic, although those with primary infection are more likely to be symptomatic than those with a recurrent infection. Signs and symptoms of CMV infection in pregnant women include:[6][22][23][24]

Symptoms in the Neonate

Infants with congenital CMV can be asymptomatic at birth. However, one or more of these symptoms may be present:[4][6][14][25][26][27][28][29][30]

Physical Examination

Physical examination findings in infants with congenital CMV infection include:[4][6][14][25][26][27][28][29][30]

Organ System Findings Suggestive of
General Appearance Small for gestational age (SGA)
Skin Skin lesions of several sizes (petechiae and purpura) Thrombocytopenic purpura
Yellow discoloration of the skin and mucous membranes Obstructive jaundice
Eyes Small eyes Microphthalmia
Clouding of the corneas Cataracts
Chorioretinitis
Yellow discoloration of the sclera Obstructive jaundice
Ears Sensorineural hearing loss
Heart Myocarditis
Abdomen Hepatosplenomegaly (HSM)
Neurological Small head circumference Microcephaly
Seizures

Laboratory Investigations

Laboratory findings in infants with congenital CMV infection include:[14][21][26][30][31][32]

Electrocardiogram

There are no ECG findings in infants with congenital CMV, unless they have associated myocarditis.

Chest X-Ray

Infants with congenital CMV have a normal chest x-ray, unless they have associated myocarditis.

CT

The following CT scan findings may be seen in patients with congenital CMV:[21][33][34][35]

MRI

MRI findings are similar to those seen on CT scan.[21][33][34][35][36]

Echocardiography

Echocardiography findings in infants with congenital CMV may be seen if they have associated myocarditis.

Ultrasound

Prenatal Ultrasound

Various findings may be seen during a routine prenatal ultrasound in a suspected case of congenital CMV infection. However, none of these findings are specific.[6][37][38][39][40][41][42][43][44][45][46][47][48][49][50]

Anomaly Possible Findings
Amniotic Fluid
Placenta
General Fetal
Brain
Heart
Gastrointestinal/ Abdominal

Other Diagnostic Studies

Serology in Mother

The following antibodies can be ordered in a pregnant woman to check the immunity status of the mother:[51]

  • IgM antibodies against CMV: detection of anti-CMV IgM antibodies alone is not a reliable means for diagnosis, because there is a high false-positive rate
  • IgG antibodies against CMV: IgG antibodies alone do not eliminate the potential for congenital CMV infection, as some infections can result from re-infection with a different strain of CMV, as well as reactivation of the latent virus
  • IgG avidity against CMV: it is a more reliable measure to detect a primary infection, as it is a measure of antibody maturity

Isolation of the Virus in the Fetus or Infant

CMV virus can be isolated or cultured from the following:[52]

Medical Therapy

Medical therapy in infants with congenital CMV infection should only be targeted towards symptomatic patients. One of the following regimens may be followed:[53][54][55][56]

  • IV Ganciclovir: should be administered to neonates with life-threatening complications. The drug is administered intravenously at a dose of 6mg/kg per dose every 12 hours. Patients are usually maintained on this drug for 2-6 weeks and can be switched to oral Valganciclovir if they are stable.
  • Oral Valganciclovir: usually administered to clinically stable neonates. The drug is given at a dose of 16mg/kg every 12 hours, usually for a period of 6 months.
  • Antiviral drugs are thought to improve auditory outcomes in infants with congenital CMV infection. However, they have no impact on neurological outcome.
  • Antiviral drugs should not be administered to asymptomatic infants.

Surgery

There is no role for surgery in the treatment of congenital CMV.

Primary Prevention

  • The following measures are recommended by the CDC to decrease the risk of congenital CMV among pregnant women or young women planning on becoming pregnant:[6]
    • Thoroughly washing hands with soap and warm water after activities such as changing diapers, feeding or bathing a young child, wiping a child's nose or handling a child's toys
    • Avoid sharing food, drinks or utensils with young children
    • Avoid sharing a toothbrush with young children
    • Avoid contact with saliva when kissing a young child
    • Clean surfaces that come in contact with a child's urine and saliva
  • Treatment of a pregnant woman with primary CMV infection with CMV hyperimmune globulin (HIG) has been tried, but its efficacy has not been proven.[57]

Secondary Prevention

Secondary prevention in infants with congenital CMV is aimed at long-term follow-up to detect any late-onset complications, such as developmental delay and sensorineural hearing loss. In addition, measures such as physical and occupational therapy, as well as audiology amplification should be implemented.[57]

References

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