Cytomegalovirus

Cytomegalovirus is the most common infectious cause and the second most common overall cause of congenital malformation in Australia. However, there is limited evidence to support universal testing of pregnant women for cytomegalovirus. As cytomegalovirus may be transmitted to the baby and can have serious consequences, the current focus is on giving women advice about hygiene measures that help to reduce their risk of infection during pregnancy.

44.1 Background

Cytomegalovirus is a member of the herpes virus family transmitted by contact with saliva, urine or genital secretions. Most people who acquire the virus after birth experience few or no symptoms. Cytomegalovirus remains latent (dormant) in the host for their lifetime after primary infection. Cytomegalovirus may become active again particularly during times of compromised immunity, including pregnancy. Congenital cytomegalovirus (infection of the baby that is present at birth) is the most frequent infectious cause of newborn disability in developed countries including Australia Rawlinson et al 2017.

44.1.1 Incidence

Transmission

Vertical transmission (spread of infection from mother to child) may occur across the placenta resulting in congenital infection in the baby Naing et al 2016. Mother-to-child transmission rates of cytomegalovirus are higher for primary maternal infection (30-35%) than reactivated (non-primary) infection or reinfection (1-2%) Kenneson & Cannon 2007; Wang et al 2011. However, reactivation or reinfection during pregnancy represents the higher burden of disease due to the high prevalence of past cytomegalovirus infection in women of childbearing age, and frequent reactivation and reinfection during pregnancy Manicklal et al 2013; Wang et al 2011.

Congenital infection

The birth prevalence of congenital cytomegalovirus infection in developed countries has been estimated at 0.64%, of whom approximately 10% are symptomatic at birth and a similar number develop symptoms before 5 years of age Kenneson & Cannon 2007. Based on average global figures in all socioeconomic groups, it has been estimated that each year approximately 400 children in Australia will be born with or develop cytomegalovirus-related disease resulting from primary or non-primary maternal infection Naing et al 2016.

Risk factors for transmission

Cytomegalovirus is a highly prevalent infection in the general population; seropositivity prevalence in adult women ranges between 40% and 90%, with the highest prevalence occurring in individuals from lower socioeconomic background Naing et al 2016. Cytomegalovirus transmission occurs via body fluids including saliva and urine. Transmission via objects contaminated with body fluids (eg utensils such as drink bottles, dummies/soothers) occurs between individuals Naing et al 2016. Children, when infected in the first few years of life, can shed virus in urine and saliva for many years either continuously or intermittently. Cytomegalovirus therefore spreads readily in settings where preschool-aged children are concentrated Manicklal et al 2013; Zheng et al 2018. This means that there is an increased risk of infection for seronegative pregnant women who have a young child in the home or who work in child care centres.

44.1.2 Risks associated with cytomegalovirus during pregnancy

Adverse effects on the developing baby include late miscarriage, stillbirth, hydrops and growth restriction McCarthy et al 2011. Approximately 10% of babies infected with cytomegalovirus in utero will have symptoms at birth (including rash, microcephaly, hepatosplenomegaly) and are at high risk of developing sensorineural hearing loss (35%) or cognitive deficits (up to 60%), other neurodevelopmental disabilities (epilepsy and cerebral palsy) or death (4%) Alarcon et al 2013; Manicklal et al 2013; McMullan et al 2011; Munro et al 2005; Smithers-Sheedy et al 2017. Infants with cytomegalovirus who are born without symptoms (“asymptomatic congenital cytomegalovirus”) are at risk of later onset of symptoms, in particular hearing loss (5–15%) Goderis et al 2014 and possibly neurodevelopmental abnormality. Asymptomatic infants without hearing loss are expected to have the best outcome Bartlett et al 2017; Lanzieri et al 2017. In developed countries, congenital cytomegalovirus accounts for approximately 20% of congenital hearing loss Dahl et al 2013; Dollard et al 2007; Rawlinson et al 2018.
The risk for adverse outcomes and/or long-term sequelae is highest in infants born to mothers with primary infection in the first half of pregnancy (approximately 10% overall) Manicklal et al 2013 although severe clinical outcomes also occur in infants of mothers with reactivation/reinfection Hadar et al 2017.
 

44.2 Discussing reducing the risk of cytomegalovirus

Awareness of cytomegalovirus infection in pregnancy is low in Australia among pregnant women (Lazzaro et al 2018) and health professionals (Shand et al 2018). Knowledge about cytomegalovirus among women who are pregnant or planning a pregnancy is limited to one in six women (Lazzaro et al 2018) and only one in ten health professionals routinely discuss cytomegalovirus prevention with pregnant women (Shand et al 2018).

Prevention through hygiene and behavioural interventions reduces maternal infection during pregnancy (Adler et al 1996; Hamilton et al 2014). Provision of information regarding congenital cytomegalovirus prevention strategies to pregnant women improves their knowledge, is acceptable to them and results in no significant increased anxiety (Lazzaro et al 2018).

Women need to be given advice about prevention strategies regardless of their serological status. Women who are aware of the cytomegalovirus negative status are more likely to adhere to prevention strategies (Adler et al 1996).

Hygiene precautions and behavioural interventions to prevent cytomegalovirus infection in pregnant women

• Do not share food, drinks, or utensils used by young children 
• Do not put a child’s dummy/soother/pacifier in your mouth 
• Avoid contact with saliva when kissing a child 
• Thoroughly wash hands with soap and water for 15–20 seconds, especially after changing nappies/diapers, feeding a young child, or wiping a young child’s nose or saliva 
• Other precautions that can be considered, but are likely to less frequently prevent infection, include cleaning toys, countertops, and other surfaces that come into contact with children’s urine or saliva, and not sharing a toothbrush with a young child

Source: Rawlinson et al 2017.

44.3 Testing for cytomegalovirus

44.3.1 Diagnostic accuracy of tests for cytomegalovirus

Up to 50% of maternal cytomegalovirus infections have nonspecific clinical manifestations, and most remain undetected unless specific serological testing is undertaken (Munro et al 2005). The combination of serology tests for cytomegalovirus-specific immunoglobulin (Ig)M, IgG and IgG avidity provide improved distinction between primary and secondary maternal infections and better define timing of infection (Naing et al 2016).

44.3.2 Universal versus targeted testing

An International Congenital Cytomegalovirus Recommendations Group Rawlinson et al 2017 noted that universal testing of pregnant women for primary cytomegalovirus infection is not recommended. The consensus document recommends that cytomegalovirus serology tests cytomegalovirus-specific IgG, IgM, and IgG avidity should be offered when a pregnant woman develops an illness, typically fever, fatigue, and headache, not attributable to another specific infection, and/or when imaging findings (ultrasound or magnetic resonance imaging [MRI]) are suggestive of fetal cytomegalovirus infection Rawlinson et al 2017.

44.3.3 Risks and benefits of maternal testing

Maternal testing to identify primary cytomegalovirus infection in pregnancy may allow for early identification of infected infants. Some countries perform more extensive testing of pregnant women Lim & Lyall 2017. However, several issues arise with extensive testing: difficulties in accurate diagnosis, absence of effective interventions in preventing transmission of cytomegalovirus from mothers with primary cytomegalovirus infection to their infant, reinfection or reactivation resulting in congenital infection, and the challenges in providing definite prognosis to an individual mother. Therefore, universal testing of asymptomatic pregnant women is not recommended Lim & Lyall 2017.

Conclusions on the cost-effectiveness of testing for cytomegalovirus are currently limited by insufficient evidence on the effectiveness of treatments in preventing congenital cytomegalovirus (see Section 44.3.4) Gantt et al 2016. 
 

44.3.4 Caring for a woman with a positive result

Cytomegalovirus hyperimmune globulin and intravenous immunoglobulin treatment do not significantly reduce the risk of congenital infection Blazquez-Gamero et al 2017; Hamilton et al 2014; Revello et al 2014. The evidence for cytomegalovirus antiviral therapy as prophylaxis or treatment of pregnant women is too limited for conclusions to be drawn Hamilton et al 2014; Leruez-Ville et al 2016.

Given the absence of an effective treatment, it is advisable to seek expert advice, including regarding assessment of the baby after the birth.

44.4 Practice summary: cytomegalovirus

When

Early in pregnancy.

Who

• Midwife
• GP
• obstetrician
• Aboriginal and Torres Strait Islander Health Practitioner
• Aboriginal and Torres Strait Islander Health Worker
• multicultural health worker
• infectious disease specialist.

What

• Discuss transmission of cytomegalovirus
  Explain that becoming infected with cytomegalovirus during pregnancy can lead to the infection being transmitted to the baby, babies born with cytomegalovirus infection at risk of impaired hearing and developmental delay.
• Take a holistic approach
  Explain that avoiding contact with a young child’s saliva and frequent hand washing are the most important measures in reducing infection with cytomegalovirus and are especially important after contact with objects contaminated with urine or saliva.
• Document and follow-up
  If a woman is tested for cytomegalovirus, tell her the results and note them in her antenatal record. If a woman has a result suggestive of recent infection, seek advice or referral to a health professional with appropriate expertise in infections in pregnancy.

44.5 Resources

• SA Perinatal Practice Guidelines Workgroup (2014) Cytomegalovirus in pregnancy. In: South Australian Perinatal Practice Guidelines. Adelaide: SA Health. 
• Palasanthiran P, Starr M, Jones C et al (2014) Management of perinatal infections. Sydney: Australasian Society for Infectious Diseases (ASID).