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Pregnancy Care Guidelines

44 Cytomegalovirus

There is limited evidence to support testing for cytomegalovirus during pregnancy. As cytomegalovirus may be transmitted to the baby and can have serious consequences, the focus is on giving women advice about hygiene measures that reduce their risk of infection.

44.1 Background

Cytomegalovirus is a member of the herpes virus family transmitted by contact with saliva, urine or genital secretions (Gilbert 2002). Most people who acquire the virus after birth experience few or no symptoms. Cytomegalovirus remains latent in the host after primary infection and may become active again, particularly during times of compromised immunity including pregnancy.

44.1.1 Incidence

  • Maternal immunity: European studies (Alanen et al 2005; Gaytant et al 2005; Naessens et al 2005; Picone et al 2009; Enders et al 2012a) estimate an incidence of cytomegalovirus immunity in pregnant women of 41–56%, with incidence as high as 98.3% among Turkish women (Uysal et al 2012) and 100% among Pakistani immigrants in Norway (Bjerke et al 2011). A Japanese study (Tagawa et al 2010) found an incidence of 87.3%.
  • Transmission: Rates of mother-to-child transmission vary depending on whether the maternal infection was primary or secondary. Low-level evidence suggests a transmission rate of 30–50% after primary infection, and 0.5–3.0% following secondary infection (Burny et al 2004; Coll et al 2009; Kenneson et al 2007; Leung 2003; Ornoy & Diav-Citrin 2006; Yinon et al 2011).
  • Congenital infection: The overall prevalence of congenital cytomegalovirus infection at birth is estimated to be 0.62–0.70% (Schlesinger et al 2003; Dollard et al 2007; Kenneson et al 2007; Naessens et al 2005). Congenital cytomegalovirus in Australia is diagnosed in 4.02 per 100,000 live births, with confirmed diagnoses in 15 infants in 2007 and 34 infants in 2008 (Ridley et al 2008).
  • Risk factors: The evidence suggests that cytomegalovirus infection during pregnancy is more common among women of lower socioeconomic status (1.2%) than among women of higher socioeconomic status (0.39%) (Dollard et al 2007). Evidence of primary infection (seroconversion) is also more likely in this group (Gaytant et al 2005). Frequent and prolonged contact with a child less than 3 years of age (eg as parent or child care worker) increases the risk of infection as cytomegalovirus is shed for long periods of time by children in this age group (Alder 2011).

44.1.2 Risks associated with cytomegalovirus during pregnancy

  • The most common cause of congenital infection in developed countries, mother-to-child transmission of cytomegalovirus, occurs in around 40% of primary infections during pregnancy (McCarthy et al 2011). Adverse effects on the developing baby include late miscarriage and growth restriction (McCarthy et al 2011). About 10% of infants with congenital cytomegalovirus infection display manifestations at birth (including growth restriction, abnormal brain development, impaired hearing, inflammation of the choroid and retina) and are at risk of neurological consequences, including cognitive and motor deficits, hearing and visual impairments (McCarthy et al 2011).
  • While the risk of transmission increases with gestational age, babies infected early in pregnancy have a greater risk of severe symptoms (Feldman et al 2011; Enders et al 2012b).

44.2 Testing for cytomegalovirus

Conclusions on the value of antenatal testing for cytomegalovirus are limited by a lack of evidence on the appropriate timing of testing, the prognosis for an infected baby and the efficacy of treatments in preventing mother-to-child transmission. Routine maternal testing for cytomegalovirus is not recommended in the United States (CDC 2008), Canada (Yinon et al 2010) or the United Kingdom (NICE 2008).

44.2.1 Diagnostic accuracy of tests

Cytomegalovirus is diagnosed by isolation of the virus from body fluids, molecular testing for cytomegalovirus genome by PCR and detection of cytomegalovirus antibodies (McCarthy et al 2011). To determine whether primary infection occurred before or during pregnancy, antibody detection needs to occur at around 12–16 weeks (Enders et al 2013). The heterogeneity of studies identified (Parmigiani et al 2003; Khare et al 2004; De Paschale et al 2010; Gabbay-Ben Ziv et al 2012; Goncé et al 2012; Peled et al 2011; Sonoyama et al 2012) makes it difficult to comment on the diagnostic accuracy of one approach to testing over another.

44.2.2 Risks and benefits of testing

There is no high-level evidence on the benefits and risks of testing. Narrative reviews suggest that:

  • possible benefits include (Burny et al 2004; Demmler 2005; ECCI 2006; Nyholm & Schleiss 2010):
    • identification of women at risk of primary infection enabling provision of prevention advice
    • diagnosis of infection during pregnancy
    • monitoring of the pregnancy and the option of diagnostic testing of the baby for women with known infection
    • the opportunity to terminate the pregnancy if fetal infection is detected early in the pregnancy
    • early commencement of neonatal antiviral treatment
  • risks or limitations include (Burny et al 2004; ECCI 2006; Coll et al 2009; Nyholm & Schleiss 2010; Lazzarotto et al 2011; Nigro & Adler et al 2004):
    • maternal anxiety
    • lack of evidence on the appropriate timing of testing as the virus may be acquired and affect the developing baby throughout pregnancy
    • the potential for false positive results
    • difficulties in determining whether maternal infection is primary or secondary
    • lack of an effective vaccine or treatment
    • potential harm from diagnostic testing of the baby (eg amniocentesis-related miscarriage)
    • lack of predictive certainty that an infected baby will be symptomatic at birth.

Conclusions on the cost-effectiveness of testing for cytomegalovirus are limited by insufficient evidence on the effectiveness of treatments in preventing congenital cytomegalovirus (Cahill et al 2009).

Recommendation

  • Consensus-based
  • XLIV

Only offer testing for cytomegalovirus to pregnant women if they come into frequent contact with large numbers of very young children (eg child care workers). 

Approved by NHMRC in June 2014; expires June 2019 UNDER REVIEW

44.2.3 Availability of safe and effective treatments

The evidence is insufficient to assess whether any interventions prevent mother-to child transmission or adverse outcomes for the congenitally infected infant (McCarthy et al 2011). Low-level evidence suggests some benefit from maternal intravenous hyperimmunoglobulin in preventing and treating congenital cytomegalovirus infection (Buxman et al 2012; Nigro et al 2012; Polilli et al 2012; Visentin et al 2012; Yamada et al 2012). Two RCTs to test the efficacy of hyperimmunoglobulin as passive immunisation are in progress.

44.3 Discussing cytomegalovirus prevention

Studies have identified low levels of knowledge about cytomegalovirus and its prevention among women (Ross et al 2008; Cannon et al 2012; Cordier et al 2012) and that health professionals may not give advice about prevention (CDC 2008).

A systematic review (Harvey & Dennis 2008) found that infection rates consistently decreased as cytomegalovirus education and support increased. These findings are supported by other lower level studies (Adler et al 2004; Picone et al 2009; Vauloup-Fellous et al 2009; Cordier et al 2012).

Providing advice to pregnant women about preventing cytomegalovirus acquisition through hygiene measures is recommended in the United States (CDC 2008). The NHMRC recommends that women of childbearing age working with children pay particular attention to good hand hygiene after contact with urine or saliva, especially after changing nappies or assisting in toilet care (NHMRC 2013).

Recommendation

  • Consensus-based
  • XLV

Advise pregnant women about hygiene measures to prevent cytomegalovirus infection such as frequent hand washing, particularly after exposure to a child’s saliva or urine. 

Approved by NHMRC in June 2014; expires June 2019 UNDER REVIEW

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.
  • Take a holistic approach
    Explain that frequent hand washing is the most important measure in controlling the spread of cytomegalovirus and is especially important after contact with articles 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 positive result, seek advice or referral to a health professional with appropriate expertise.

44.5 Resources

  • SA Perinatal Practice Guidelines Workgroup (2014) Cytomegalovirus in pregnancy. In: South Australian Perinatal Practice Guidelines. Adelaide: SA Health.

References

  • Adler S, Finney J, Manganello A et al (2004) Prevention of child-to-mother transmission of cytomegalovirus among pregnant women. J Pediatr 145 (4): 485–91.
  • Alanen A, Kahala K, Vahlberg T et al (2005) Seroprevalence, incidence of prenatal infections and reliability of maternal history of varicella zoster virus, cytomegalovirus, herpes simplex virus and parvovirus B19 infection in South- Western Finland. BJOG 112(1): 50–56.
  • Bjerke SEY, Vangen S, Holter E et al (2011) Infectious immune status in an obstetric population of Pakistani immigrants in Norway. Scand J Pub Health 39(5): 464–70.
  • Burny W, Liesnard C, Donner C et al (2004) Epidemiology, pathogenesis and prevention of congenital cytomegalovirus infection. Exp Rev Anti-Infect Ther 2(6): 881–94.
  • Buxman H, Von Stackelberg OM, Schloesser RL et al (2012) Use of cytomegalovirus hyperimmunoglobulin for prevention of congenital cytomegalovirus disease: a retrospective analysis. J Perinat Med 40(4): 440–46.
  • Cahill A, Odibo A, Stamilio D et al (2009) Screening and treating for primary cytomegalovirus infection in pregnancy: where do we stand? A decision-analytic and economic analysis. Am J Obstet Gynecol 201(5): 466.
  • Cannon MJ, Westbrook K, Levis D et al (2012) Awareness of and behaviors related to child-to-mother transmission of cytomegalovirus. Prevent Med 54(5): 351–57.
  • CDC (2008) Knowledge and practices of obstetricians and gynecologists regarding cytomegalovirus infection during pregnancy -- United States, 2007. Centre for Disease Control and Prevention. MMWR 57(3): 65–68.
  • Coll O, Benoist G, Ville Y et al (2009) Guidelines on CMV congenital infection. J Perinat Med 37(5): 433–45.
  • Cordier AG, Guitton S, Vauloup-Fellous C et al (2012) Awareness of cytomegalovirus infection among pregnant women in France. J Clin Virol 53(4): 332–37.
  • De Paschale M, Agrappi C, Manco M et al (2010) Positive predictive value of anti-HCMV IgM as an index of primary infection. J Virol Methods 168(1-2): 121–25.
  • Demmler G (2005) Screening for congenital cytomegalovirus infection: a tapestry of controversies. J Paediatr 146: 162–64.
  • Dollard S, Grosse S, Ross D (2007) New estimates of the prevalence of neurological and sensory sequelae and mortality associated with congenital cytomegalovirus infection. Rev Med Virol 17(5): 355–63.
  • Enders G, Daiminger A, Baeder U et al (2012b) Intrauterine transmission and clinical outcome of 248 pregnancies with primary cytomegalovirus infection in relation to gestational age. J Clin Virol 52(3): 244–46.
  • Enders G, Daiminger A, Baeder U et al (2013) The value of CMV IgG avidity and immunoblot for timing the onset of primary CMV infection in pregnancy. J Clin Virol 56(2): 102–07.
  • Enders G, Daiminger A, Lindemann L et al (2012a) Cytomegalovirus (CMV) seroprevalence in pregnant women, bone marrow donors and adolescents in Germany, 1996-2010. Med Microbiol Immunol 201(3) :303–09.
  • ECCI (2006) European Congenital Cytomegalovirus Initiative Recommendations. Accessed 10 August 2018.
  • Feldman, B, Yinon Y, Tepperberg Oikawa M et al (2011) Pregestational, periconceptional, and gestational primary maternal cytomegalovirus infection: prenatal diagnosis in 508 pregnancies. Am J Obstet Gynaecol 52(3): 244–46.
  • Gabbay-Ben Ziv R, Yogev, Y, Peled Y et al (2012) Congenital cytomegalovirus infection following antenatal negative diagnostic amniotic fluid analysis-A single center experience. J Maternal-Fetal Neonat Med 25(9): 1787–90.
  • Gaytant M, Galama J, Semmekrot B et al (2005) The incidence of congenital cytomegalovirus infections in The Netherlands. J Med Virol 76(1): 71–75.
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  • Goncé A, Marcos MA, Borrell A et al (2012) Maternal IgM antibody status in confirmed fetal cytomegalovirus infection detected by sonographic signs. Prenat Diag 32(9): 817–21.
  • Harvey J & Dennis C (2008) Hygiene interventions for prevention of cytomegalovirus infection among childbearing women: systematic review. J Adv Nurs 63(5): 440–50.
  • Kenneson A & Cannon M (2007) Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection. Rev Med Virol 17(4): 253–76.
  • Khare M, Sharland M, Manyonda I et al (2004) Use of serial maternal urine cytomegalovirus PCR to detect primary CMV infection in seronegative women. J Virol Methods 19: 31–35.
  • Lazzarotto T, Guerra B, Gabrielli L et al (2011) Update on the prevention, diagnosis and management of cytomegalovirus infection during pregnancy. Clin Microbiol Infect 17(9): 1285–93.
  • Leung, A, Sauve R, Davies H (2003) Congenital cytomegalovirus infection. J Nat Med Assoc 95(3): 213–18.
  • McCarthy F, Giles M, Rowlands S et al (2011) Antenatal interventions for preventing the transmission of cytomegalovirus (CMV) from the mother to fetus during pregnancy and adverse outcomes in the congenitally infected infant. Cochrane Database Of Systematic Reviews.
  • Naessens A, Casteels A, Decatte L et al (2005) A serologic strategy for detecting neonates at risk for congenital cytomegalovirus infection. J Paediatr 146(2): 194–97.
  • NHMRC (2013) Staying Healthy in Child Care Preventing Infectious Diseases in Child Care. Commonwealth of Australia.
  • NICE (2008) Antenatal Care. Routine Care for the Healthy Pregnant Woman. National Collaborating Centre for Women’s and Children’s Health. Commissioned by the National Institute for Health and Clinical Excellence. London: RCOG Press
  • Nigro G & Adler S(2011) Cytomegalovirus infections during pregnancy. Curr Op Obstet Gynecol 23(2): 123–28.
  • Nigro G, Adler SP, Parruti G et al (2012) Immunoglobulin therapy of fetal cytomegalovirus infection occurring in the first half of pregnancy – a case control study of the outcome in children. J Infect Dis 205(2): 215–27.
  • Nyholm J & Schleiss M (2010) Prevention of maternal cytomegalovirus infection: Current status and future prospects. Int J Women’s Health 2(1): 23–35.
  • Ornoy A & Diav-Citrin O (2006) Fetal effects of primary and secondary cytomegalovirus infection in pregnancy. Reprod Toxicol 21(4): 399–409.
  • Parmigiani S, Barini R, Costa S et al (2003) Accuracy of the serological ELISA test compared with the polymerase chain reaction for the diagnosis of cytomegalovirus infection in pregnancy. Sao Paulo Med J 121(3): 97–101.
  • Peled Y, Yogev Y, Oron G et al (2011) Suggested algorithm for cytomegalovirus surveillance in low-risk pregnancies. J Maternal-Fetal Neonat Med 24(11): 1353–56.
  • Picone O, Vauloup-Fellous C, Cordier A et al (2009) A 2-year study on cytomegalovirus infection during pregnancy in a French hospital. BJOG 116: 818–23.
  • Polilli E, Parruti G, D’Arcangelo F et al (2012) Preliminary evaluation of the Safety and Efficacy of Standard Intravenous Immunoglobulins in Pregnant Women with Primary Cytomegalovirus Infection. Clin Vaccine Immunol 19(12):1991– 93.
  • Ridley G, Zurynski Y, Elliot E (2008) Australian Paediatric Surveillance Unit Research Report 2007–2008. Sydney: Australian Paediatric Surveillance Unit.
  • Ross D, Victor M, Sumartojo E et al (2008) Women’s knowledge of congenital cytomegalovirus: Results from the 2005 Healthstyles survey. J Women’s Health 17(5): 849–58.
  • Schlesinger Y, Halle D, Eidelman A et al (2003) Urine polymerase chain reaction as a screening tool for the detection of congenital cytomegalovirus infection. Arch Dis Child 88(5): F371–74.
  • Sonoyama A, Ebina Y, Morioka I et al (2012) Low IgG Avidity and Ultrasound Fetal Abnormality predict Congenital Cytomegalovirus Infection. J Med Virol 84(12): 1928–33.
  • Tagawa M, Minematsu T, Masuzaki H et al (2010) Seroepidemiological survey of cytomegalovirus infection among pregnant women in Nagasaki, Japan. Pediatr Int 52(3): 459–62.
  • Uysal A, Taner CE, Cuce M et al (2012) Cytomegalovirus and rubella seroprevalence in pregnant women in Izmir/Turkey: follow-up and results of pregnancy outcome. Arch Gynecol Obstet 286(3): 605–08.
  • Vauloup-Fellous C, Picone O, Cordier A-G et al (2009) Does hygiene counseling have an impact on the rate of CMV primary infection during pregnancy? Results of a 3-year prospective study in a French hospital. J Clin Virol 46(4): S49–53.
  • Visentin S, Manara R, Milanese L et al (2012) Early primary cytomegalovirus infection in pregnancy: maternal hyperimmunoglobulin therapy improves outcomes among infants at 1 year age. Clin Infect Dis 55(4): 497–503.
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Last updated: 
20 November 2018