Cytomegalovirus in Pregnancy

Human Cytomegalovirus (CMV) is a common herpesvirus that is rarely serious in healthy adults.

Despite this, it is the most common cause of serious congenital birth defects. And, primary intrauterine infections are second only to Down’s Syndrome as a known cause of mental retardation.

CMV is also associated with complications in immunocompromised individuals (such as HIV-infected people and transplant recipients).

Since infections are asymptomatic or non-specific to CMV, laboratory methods are the only way to diagnose infection or to determine immune status.¹

World map showing CMV prevalence rates by region.
There is wide variation in prevalence rates based on geography:
Africa: 82-100% | Australia/Western Europe/USA: 42-85% | South America: 81-98%

Stages of CMV Infection

Primary Infection: occurs when the CMV virus infects a previously uninfected (or seronegative) individual.

Latency: After primary infection, CMV establishes itself in the body in latent form. An important part of this latency is that the virus remains indefinitely and can be reactivated (to produce infection) by immunosuppression or other stimuli.

Non-primary Infection: Non-primary, or Secondary, CMV infection occurs when a previously infected individual experiences a reactivation of a previous CMV infection or a reinfection with a new strain of CMV.

Routes of Transmission

CMV is spread from person-to-person by close contact with body fluids that contain the virus. Situations in which transmission of CMV often occurs include the following:

Intrauterine - If primary maternal infection occurs during pregnancy, there is about 1 chance in 3 that the fetus will be infected.
Daycare - Preschool-aged children in close daily contact often spread CMV to each other, increasing the number of infected children and exposed parents.
Child Rearing - Infants and young children with CMV infection shed virus in urine and saliva for many months. Often they can transmit CMV to their susceptible caregivers, including their mothers, fathers, and child care workers.
Intimate Contact - CMV is present in saliva and genital secretions of men and women and can be transmitted during sexual activity or intimate contact.
Breastfeeding - CMV is commonly spread from mother to child through breastfeeding. This can only occur if the mother has been infected by CMV. With rare exceptions, infants who acquire CMV by breastfeeding do not have signs or symptoms.
During Birth - If CMV is present in the birth canal, it can be transmitted from mother to baby (intrapartum transmission). These infections do not cause disease in the baby unless it is very small and premature or has an impaired immune system.

Symptoms of Maternal CMV Infection

Fever
Headache
Fatigue
Myalgia
Sore throat

Since these symptoms are not specific to CMV, laboratory methods are required to diagnose maternal CMV infection.

Congenital CMV Infection

Transmission of the virus to the fetus most frequently occurs during primary maternal CMV infection.

Congenital Symptoms:

Growth retardation at birth
Central Nervous System abnormalities
Microcephaly (small head size)
Mental retardation
Chorioretinitis and optic atrophy
Hearing Loss / Sensorineural deafness
Liver and spleen abnormalities leading to abdominal distention
Fluid collection around lungs and heart
Thrombocytopenic Purpura, Haemolytic Anemia
Late sequelae in individuals asymptomatic at birth - hearing defects and reduced intelligence
Petechiae

Incidence of Handicaps

Incidence of Severe Sequale & Handicaps Following Primary Maternal Infection²

	Week of Gestation
	4-22	16-27	23-40
Congenital infections	51%	60%	44%
Symptoms at birth	12%	16%	0%
Severe handicaps	29%	0%	0%

The most severe handicaps result from infection acquired during the 4th to 22nd week of gestation.

Schematic overview of CMV Infection

Primary vs. Non-Primary Maternal Infection

There is a considerable difference between primary and non-primary infection of the mother in the likelihood of passing congenital CMV on to her unborn child.

In a primary infection, there is an 30-40% chance of passing the virus on to the fetus; a secondary infection carries a 0.5-1% chance.³

Therefore distinguishing between an acute infection and a reactivation is of paramount importance.

CMV Laboratory Tests

IgG: the antibody that provides the majority of immunity in response to infection. IgG antibodies remain detectable in the body long after infection and can be measured to determine if someone has ever been exposed to the infection.

IgG Avidity: is used to to help distinguish between a primary and non-primary infection. It is a measurement of the functional binding affinity of an immunoglobulin.
• High avidity indicates non-primary infection
• Low avidity indicates primary infection

Individuals at Risk

Persons at highest risk for acquiring CMV are those that have not been previously infected and, therefore, have no antibody to CMV. The risk of passing on a congenital CMV infection is very high among seronegative pregnant women who become infected with CMV.

High risk groups:

Seronegative pregnant women, especially those with children in daycare
Younger mothers
Parents of children who are shedding CMV virus

Prevention

The US CDC recommends⁴ the following preventative measures for women who are pregnant.

Wash hands with soap and water often and thoroughly, especially when in contact with young children (diaper changes, etc)
Avoid kissing young children on the mouth
Do not share food or eating utensils with young children
If you are employed in a childcare setting, you can reduce your risk by working with children who are older than 2 ½, especially if you do not know your CMV status

CMV Resources

Congenital Learning Guide (PDF, 2217 KB): Written by leading international experts in the field of congenital diseases, this new Learning Guide is aimed at healthcare professionals seeking information about congenital Rubella, Toxoplasma and CMV infections.
United States Centers for Disease Control and Prevention - Cytomegalovirus Home Page: The US CDC features a wealth of information on its CMV Home Page targeted at both patients and caregivers.

Documents linked on this page may be in PDF format.
A free reader is available here via Adobe Systems.

Citations

Source: Dr. T. Lazzarotto, Univ. of Bologna
Source: Stagno et al., JAMA,1986
Guerra B, Simonazzi G, Banfi A, et al. Impact of diagnostic and confirmatory tests and prenatal counseling on the rate of pregnancy termination among women with positive cytomegalovirus immunoglobulin M antibody titers. Am J Obstet Gynecol 2007;196:221.e1-221.e6.
What Women Should Know About Cytomegalovirus, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Control and Prevention