Clinical Practice Guidelines Antenatal Care — Module II
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- Risks associated with cytomegalovirus during pregnancy
- Screening for cytomegalovirus
- Diagnostic accuracy of tests
- Risks and benefits of screening
- Availability of safe and effective treatments
- Discussing cytomegalovirus prevention
- Practice summary: cytomegalovirus
9.10CytomegalovirusThere is limited evidence to support screening 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. BackgroundCytomegalovirus 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. IncidenceMaternal 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). Risks associated with cytomegalovirus during pregnancyThe 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). Screening for cytomegalovirusSummary of the evidenceConclusions on the value of antenatal screening for cytomegalovirus are limited by a lack of evidence on the appropriate timing of screening, the prognosis for an infected baby and the efficacy of treatments in preventing mother-to-child transmission. Routine maternal screening for cytomegalovirus is not recommended in the United States (CDC 2008), Canada (Yinon et al 2010) or the United Kingdom (NICE 2008). Diagnostic accuracy of testsCytomegalovirus 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 2012; Sonoyama et al 2012) makes it difficult to comment on the diagnostic accuracy of one approach to testing over another. Risks and benefits of screeningThere is no high-level evidence on the benefits and risks of screening. 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; and 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 2011): maternal anxiety; lack of evidence on the appropriate timing of screening 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); and lack of predictive certainty that an infected baby will be symptomatic at birth. Conclusions on the cost-effectiveness of screening for cytomegalovirus are limited by insufficient evidence on the effectiveness of treatments in preventing congenital cytomegalovirus (Cahill et al 2009). Consensus-based recommendation xvi Only offer screening for cytomegalovirus to pregnant women if they come into frequent contact with large numbers of very young children (eg child care workers). Availability of safe and effective treatmentsThe 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. Discussing cytomegalovirus preventionStudies have identified low levels of knowledge about cytomegalovirus and its prevention among women (Ross et al 2007; 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).
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. Practice summary: cytomegalovirus
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