Cytomegalovirus Infection: Perinatal Implications
2002; Elsevier BV; Volume: 31; Issue: 1 Linguagem: Inglês
10.1111/j.1552-6909.2002.tb00026.x
ISSN1552-6909
AutoresElizabeth G. Damato, Caitlin W. Winnen,
Tópico(s)Herpesvirus Infections and Treatments
ResumoCytomegalovirus (CMV), a member of the herpes virus family, is the most common cause of congenital infection in humans, affecting 0.5–3% of all newborns worldwide. Congenital cytomegalovirus infection is the leading infectious cause of deafness, learning disabilities, and mental retardation in children. The high prevalence of cytomegalovirus in the general population, unpredictability of transmission, and asymptomatic nature of the disease in otherwise healthy women challenge prevention and treatment efforts. Cytomegalovirus (CMV), a member of the herpes virus family, is the most common cause of congenital infection in humans, affecting 0.5–3% of all newborns worldwide. Congenital cytomegalovirus infection is the leading infectious cause of deafness, learning disabilities, and mental retardation in children. The high prevalence of cytomegalovirus in the general population, unpredictability of transmission, and asymptomatic nature of the disease in otherwise healthy women challenge prevention and treatment efforts. Cytomegalovirus (CMV) is the most common of the TORCH infections, which are infectious diseases classified together because of their potentially deleterious effects on the fetus. These include toxoplasmosis, rubella, CMV, and herpes simplex virus. CMV is considered a sexually transmitted disease, although this virus is transmitted through various routes. It has been isolated in saliva, breast milk, respiratory secretions, blood, urine, and feces, as well as in cervical secretions and semen. Transplacental transmission is also known to occur (Li and Tsutsui, 2000Li R.Y. Tsutsui Y. Growth retardation and microcephaly induced in mice by placental infection with murine cytomegalovirus.Teratology. 2000; 62: 79-85Crossref PubMed Scopus (52) Google Scholar; McCance and Huether, 1998McCance K.L. Huether S.E. Pathophysiology: The biologic basis for disease in adults and children.3rd ed. Mosby, St. Louis, MO1998Google Scholar; Nelson and Demmler, 1997Nelson C.T. Demmler G.J. Cytomegalovirus infection in the pregnant mother, fetus, and newborn infant.Clinics in Perinatology. 1997; 24: 151-160PubMed Google Scholar; Sherwen et al., 1999Sherwen L.N. Scoloveno M.A. Weingarten C.T. Maternity nursing: Care of the childbearing family.3rd ed. Appleton & Lange, Stamford, CT1999Google Scholar). The presence of maternal antibodies against this commonly asymptomatic disease does not consistently provide protection against reinfection or reactivation of the disease (Nelson and Demmler, 1997Nelson C.T. Demmler G.J. Cytomegalovirus infection in the pregnant mother, fetus, and newborn infant.Clinics in Perinatology. 1997; 24: 151-160PubMed Google Scholar; Stamos and Rowley, 1994Stamos J. Rowley A. Timely diagnosis of congenital infection.Pediatric Clinics of North America. 1994; 41: 1017-1033PubMed Google Scholar; Wong et al., 2000Wong A. Tan K.H. Tee C.S. Yeo G.S.H. Seroprevalence of cytomegalovirus, toxoplasma and parvovirus in pregnancy.Singapore Medical Journal. 2000; 41: 151-155PubMed Google Scholar). The significance of CMV infection lies in the potential transmission to the vulnerable fetus or newborn of an infected woman. Following primary CMV infection during pregnancy, approximately 40–50% of fetuses will become infected (Nelson and Demmler, 1997Nelson C.T. Demmler G.J. Cytomegalovirus infection in the pregnant mother, fetus, and newborn infant.Clinics in Perinatology. 1997; 24: 151-160PubMed Google Scholar; Stamos and Rowley, 1994Stamos J. Rowley A. Timely diagnosis of congenital infection.Pediatric Clinics of North America. 1994; 41: 1017-1033PubMed Google Scholar). An estimated 5–18% of infected newborns display evidence of CMV infection (Wong et al., 2000Wong A. Tan K.H. Tee C.S. Yeo G.S.H. Seroprevalence of cytomegalovirus, toxoplasma and parvovirus in pregnancy.Singapore Medical Journal. 2000; 41: 151-155PubMed Google Scholar). Cytomegalic inclusion disease, which has a 20–30% mortality rate, may develop in 10% of these infected newborns (Nelson and Demmler, 1997Nelson C.T. Demmler G.J. Cytomegalovirus infection in the pregnant mother, fetus, and newborn infant.Clinics in Perinatology. 1997; 24: 151-160PubMed Google Scholar; Wong et al., 2000Wong A. Tan K.H. Tee C.S. Yeo G.S.H. Seroprevalence of cytomegalovirus, toxoplasma and parvovirus in pregnancy.Singapore Medical Journal. 2000; 41: 151-155PubMed Google Scholar). Congenital malformations associated with CMV include microcephaly, cerebral calcifications, chorioretinitis and blindness, and hepatosplenomegaly (Sherwen et al., 1999Sherwen L.N. Scoloveno M.A. Weingarten C.T. Maternity nursing: Care of the childbearing family.3rd ed. Appleton & Lange, Stamford, CT1999Google Scholar). The majority of infected infants are asymptomatic at birth. Of these infants, 5–15% will experience some form of neurodevelopmental complication during early childhood (Alford et al., 1990Alford C.A. Stagno S. Pass R.F. Britt W.J. Congenital and perinatal cytomegalovirus infections.Reviews of Infectious Diseases. 1990; 12: S745-S753Crossref PubMed Scopus (299) Google Scholar; Fowler et al., 1997Fowler K.B. McCollister F.P. Dahle A.J. Boppana S. Britt W.L. Pass R.F. Progressive and fluctuating sensorineural hearing loss in children with asymptomatic congenital cytomegalovirus infection.Journal of Pediatrics. 1997; 130: 624-630Abstract Full Text Full Text PDF PubMed Scopus (410) Google Scholar; Wong et al., 2000Wong A. Tan K.H. Tee C.S. Yeo G.S.H. Seroprevalence of cytomegalovirus, toxoplasma and parvovirus in pregnancy.Singapore Medical Journal. 2000; 41: 151-155PubMed Google Scholar). Congenital CMV infection is believed to be the most common infectious cause of mental retardation, deafness, and learning disabilities in children (Demmler, 1991Demmler G.J. Summary of a workshop on surveillance for congenital cytomegalovirus disease.Reviews of Infectious Diseases. 1991; 13: 315-329Crossref PubMed Scopus (430) Google Scholar; Fowler et al., 1997Fowler K.B. McCollister F.P. Dahle A.J. Boppana S. Britt W.L. Pass R.F. Progressive and fluctuating sensorineural hearing loss in children with asymptomatic congenital cytomegalovirus infection.Journal of Pediatrics. 1997; 130: 624-630Abstract Full Text Full Text PDF PubMed Scopus (410) Google Scholar; Mehta and Hartnoll, 2001Mehta N.M. Hartnoll G. Congenital CMV with callosal lipoma and agenesis.Pediatric Neurology. 2001; 24: 222-224Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar; Stamos and Rowley, 1994Stamos J. Rowley A. Timely diagnosis of congenital infection.Pediatric Clinics of North America. 1994; 41: 1017-1033PubMed Google Scholar). This article highlights the perinatal effects and nursing implications of this serious viral infection. The most common congenital and perinatal viral infection throughout the world, CMV affects an estimated 0.5–3% of all newborns (Nelson and Demmler, 1997Nelson C.T. Demmler G.J. Cytomegalovirus infection in the pregnant mother, fetus, and newborn infant.Clinics in Perinatology. 1997; 24: 151-160PubMed Google Scholar; Sherwen et al., 1999Sherwen L.N. Scoloveno M.A. Weingarten C.T. Maternity nursing: Care of the childbearing family.3rd ed. Appleton & Lange, Stamford, CT1999Google Scholar; Stamos and Rowley, 1994Stamos J. Rowley A. Timely diagnosis of congenital infection.Pediatric Clinics of North America. 1994; 41: 1017-1033PubMed Google Scholar). For women in countries such as the Ivory Coast, Japan, and Chile, the seroprevalence of CMV is more than 90% by the age of 30. Prevalence rates in women in the United States and Western Europe range from 50–85% (Demmler, 1991Demmler G.J. Summary of a workshop on surveillance for congenital cytomegalovirus disease.Reviews of Infectious Diseases. 1991; 13: 315-329Crossref PubMed Scopus (430) Google Scholar). Seropositivity in Thailand is reported to be 100% (1). The increased seroprevalence in lower socioeconomic groups and developing countries is thought to be due to increased exposure to CMV because of crowded conditions in urban settings, increased exposure to infants and toddlers, poor hygiene, earlier onset of sexual activity, and greater number of sexual partners (Alford et al., 1990Alford C.A. Stagno S. Pass R.F. Britt W.J. Congenital and perinatal cytomegalovirus infections.Reviews of Infectious Diseases. 1990; 12: S745-S753Crossref PubMed Scopus (299) Google Scholar; Demmler, 1991Demmler G.J. Summary of a workshop on surveillance for congenital cytomegalovirus disease.Reviews of Infectious Diseases. 1991; 13: 315-329Crossref PubMed Scopus (430) Google Scholar; Martinez et al., 2001Martinez A. Castro A. Gil C. Perez C. Recent strategies in the development of new human cytomegalovirus inhibitors.Medical Research Reviews. 2001; 21: 227-244Crossref PubMed Scopus (27) Google Scholar; Wong et al., 2000Wong A. Tan K.H. Tee C.S. Yeo G.S.H. Seroprevalence of cytomegalovirus, toxoplasma and parvovirus in pregnancy.Singapore Medical Journal. 2000; 41: 151-155PubMed Google Scholar). Congenital CMV infection is the most common infectious cause of mental retardation, deafness, and learning disabilities in children. It is estimated that 0.7–6% of pregnant women develop primary CMV infection during pregnancy (Demmler, 1991Demmler G.J. Summary of a workshop on surveillance for congenital cytomegalovirus disease.Reviews of Infectious Diseases. 1991; 13: 315-329Crossref PubMed Scopus (430) Google Scholar; Sherwen et al., 1999Sherwen L.N. Scoloveno M.A. Weingarten C.T. Maternity nursing: Care of the childbearing family.3rd ed. Appleton & Lange, Stamford, CT1999Google Scholar). For childbearing women, the most important risk factor is the use of child care outside the home. Child-to-child transmission of CMV through saliva and other secretions on hands and toys puts pregnant women at risk for contracting the virus from their older children who attend day care (Alford et al., 1990Alford C.A. Stagno S. Pass R.F. Britt W.J. Congenital and perinatal cytomegalovirus infections.Reviews of Infectious Diseases. 1990; 12: S745-S753Crossref PubMed Scopus (299) Google Scholar). Reports of positive seroconversion of parents with children who are in group day care range from 21–45% (Murph et al., 1991Murph J.R. Baron J.C. Brown C.K. Ebelhack C.L. Bale J.F. The occupational risk of cytomega-lovirus infection among day-care providers.Journal of the American Medical Association. 1991; 265: 603-608Crossref Scopus (85) Google Scholar). For unknown reasons, the prevalence of maternal antibodies in a population is matched by a high rate of congenital CMV infection. In contrast to maternal antibodies for rubella and toxoplasmosis, maternal antibodies for CMV does not consistently provide protection against intrauterine transmission, although it does reduce the rate of transmission and sequelae (Nelson and Demmler, 1997Nelson C.T. Demmler G.J. Cytomegalovirus infection in the pregnant mother, fetus, and newborn infant.Clinics in Perinatology. 1997; 24: 151-160PubMed Google Scholar; Stamos and Rowley, 1994Stamos J. Rowley A. Timely diagnosis of congenital infection.Pediatric Clinics of North America. 1994; 41: 1017-1033PubMed Google Scholar). The characteristic light microscope finding of CMV infection is a large cell with round, deeply acidophilic, intranuclear, and paranuclear inclusions surrounded by a clear halo (Bachor et al., 2000Bachor E. Sudhoff H. Litschel R. Karmody C.S. The pathology of the temporal bones of a child with acquired cytomegalovirus infection: Studies by light microscopy, immunohistochemistry and polymerase-chain reaction.International Journal of Pediatric Otorhinolaryngology. 2000; 55: 215-224Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar). This causes infected cells to take on an enlarged "owls' eyes" appearance (Boyd, 1995Boyd R.F. Basic medical microbiology.5th ed. Little, Brown, Boston1995Google Scholar). CMV has strict species specificity, which limits studies of the disease as it affects humans (Alford et al., 1990Alford C.A. Stagno S. Pass R.F. Britt W.J. Congenital and perinatal cytomegalovirus infections.Reviews of Infectious Diseases. 1990; 12: S745-S753Crossref PubMed Scopus (299) Google Scholar; Li and Tsutsui, 2000Li R.Y. Tsutsui Y. Growth retardation and microcephaly induced in mice by placental infection with murine cytomegalovirus.Teratology. 2000; 62: 79-85Crossref PubMed Scopus (52) Google Scholar). Once the virus infects a cell, it can replicate and either destroy the cell or become part of the cell's DNA. Local CMV infections can persist despite subsequent CMV antibody presence. This may be caused by injury of T cells or macrophages by CMV during the primary infection (Alford et al., 1990Alford C.A. Stagno S. Pass R.F. Britt W.J. Congenital and perinatal cytomegalovirus infections.Reviews of Infectious Diseases. 1990; 12: S745-S753Crossref PubMed Scopus (299) Google Scholar; McCance and Huether, 1998McCance K.L. Huether S.E. Pathophysiology: The biologic basis for disease in adults and children.3rd ed. Mosby, St. Louis, MO1998Google Scholar). There are three condition subsets of CMV, classified by type of transmission. CMV can be transmitted transplacentally (congenital CMV) or by direct transfer of infected body fluids such as maternal genital secretions during the intrapartum (perinatal CMV) or through ingestion of infected breast milk (postnatal CMV) (Alford et al., 1990Alford C.A. Stagno S. Pass R.F. Britt W.J. Congenital and perinatal cytomegalovirus infections.Reviews of Infectious Diseases. 1990; 12: S745-S753Crossref PubMed Scopus (299) Google Scholar; McCance and Huether, 1998McCance K.L. Huether S.E. Pathophysiology: The biologic basis for disease in adults and children.3rd ed. Mosby, St. Louis, MO1998Google Scholar). Those most at risk for symptomatic infection often are immunocompromised by drugs (such as organ transplant recipients or oncology patients), disease (such as acquired immunodeficiency syndrome [AIDS]), or because of immature immune function (fetus and newborns). CMV has a particular affinity for the central nervous system, the eyes, and the liver (Stamos and Rowley, 1994Stamos J. Rowley A. Timely diagnosis of congenital infection.Pediatric Clinics of North America. 1994; 41: 1017-1033PubMed Google Scholar). Healthy infected adults may have mild and often unnoticed symptoms, but immunocompromised adults often seek care with symptoms specific to the organ or organs involved. These symptoms can include an erythematous maculopapular skin rash, chorioretinitis, colitis, adult respiratory distress syndrome, hemoptysis, and dyspnea (Kanno et al., 2001Kanno M. Chandrasekar P.H. Bentley G. Vander Heide R.S. Alangaden G.J. Disseminated cytomegalovirus disease in hosts without acquired immunodeficiency syndrome and without an organ transplant.Clinical Infectious Diseases. 2001; 32: 313-316Crossref PubMed Scopus (21) Google Scholar; Seishima et al., 2001Seishima M. Izumi T. Oyama Z. Rubella-like or morbilliform eruptions in non-immunosuppressed patients with positive IgM antibody to cytomegalovirus.British Journal of Dermatology. 2001; 144: 203-205Crossref PubMed Scopus (6) Google Scholar). CMV also has been known to trigger the onset of Guillain-Barre syndrome (Nesbitt, 2000Nesbitt I. Pregnancy, anaesthesia, and Guillain-Barre syndrome.Anaesthesia. 2000; 55: 1227-1228Crossref PubMed Scopus (4) Google Scholar). The rate of transplacental transmission of CMV from infected mother to fetus is unpredictable and appears to occur with equal frequency in all trimesters of pregnancy (Nelson and Demmler, 1997Nelson C.T. Demmler G.J. Cytomegalovirus infection in the pregnant mother, fetus, and newborn infant.Clinics in Perinatology. 1997; 24: 151-160PubMed Google Scholar). Exactly why some pregnant women with CMV infection transmit the virus in utero and others do not is unknown. Approximately 10% of infected infants will be symptomatic at birth, whereas most infants (90%) will have chronic subclinical disease (Nelson and Demmler, 1997Nelson C.T. Demmler G.J. Cytomegalovirus infection in the pregnant mother, fetus, and newborn infant.Clinics in Perinatology. 1997; 24: 151-160PubMed Google Scholar). Perinatally acquired CMV infection occurs as the fetus is exposed to infected maternal genital secretions during the birth process, by the ingestion of infected breast milk, or by contact with maternal mouth secretions. Between 40%–60% of infants who are breastfed for more than 1 month by seropositive mothers and 25%–50% who are exposed to CMV in the birth canal can become infected (Alford et al., 1990Alford C.A. Stagno S. Pass R.F. Britt W.J. Congenital and perinatal cytomegalovirus infections.Reviews of Infectious Diseases. 1990; 12: S745-S753Crossref PubMed Scopus (299) Google Scholar; Nelson and Demmler, 1997Nelson C.T. Demmler G.J. Cytomegalovirus infection in the pregnant mother, fetus, and newborn infant.Clinics in Perinatology. 1997; 24: 151-160PubMed Google Scholar). The increased popularity of breastfeeding and more common use of group day care in the United States and other developed countries may result in a resurgence of postnatally acquired CMV infection. (Demmler, 1991Demmler G.J. Summary of a workshop on surveillance for congenital cytomegalovirus disease.Reviews of Infectious Diseases. 1991; 13: 315-329Crossref PubMed Scopus (430) Google Scholar; Remington and Klein, 2001Remington J.S. Klein J.O. Infectious diseases of the fetus and newborn infant.5th ed. Saunders, Philadelphia2001Google Scholar). Healthy women of childbearing age may not notice any symptoms of primary CMV infection. Often, the first suspicion of CMV infection in a pregnant woman results from abnormalities discovered through prenatal diagnostic testing (Nelson and Demmler, 1997Nelson C.T. Demmler G.J. Cytomegalovirus infection in the pregnant mother, fetus, and newborn infant.Clinics in Perinatology. 1997; 24: 151-160PubMed Google Scholar). Table 1 lists symptoms of CMV infections in pregnant women (Inoue et al., 2001Inoue T. Matsumura N. Fukuoka M. Sagawa N. Fujii S. Severe congenital cytomegalovirus infection with fetal hydrops in a cytomegalovirus-seropositive healthy woman.European Journal of Obstetrics & Gynecology and Reproductive Biology. 2001; 95: 184-186Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar; Nelson and Demmler, 1997Nelson C.T. Demmler G.J. Cytomegalovirus infection in the pregnant mother, fetus, and newborn infant.Clinics in Perinatology. 1997; 24: 151-160PubMed Google Scholar; Sherwen et al., 1999Sherwen L.N. Scoloveno M.A. Weingarten C.T. Maternity nursing: Care of the childbearing family.3rd ed. Appleton & Lange, Stamford, CT1999Google Scholar). Recent case reports suggest that CMV infection may be responsible for persistent infertility and recurrent pregnancy losses (Nelson and Demmler, 1997Nelson C.T. Demmler G.J. Cytomegalovirus infection in the pregnant mother, fetus, and newborn infant.Clinics in Perinatology. 1997; 24: 151-160PubMed Google Scholar; Nigro et al., 2000Nigro G. Mazzocco M. Aragona C. D'Emilio C. Cosmi E.V. Hyperimmunoglobulin therapy for cytomegalovirus-associated infertility: Case reports.Fertility and Sterility. 2000; 74: 830-831Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar).Table 1Symptoms of Cytomegalovirus Infection in the Pregnant Woman• Often asymptomatic• Fever, chills• Malaise• Myalgias• Sore throat• Nausea• Coughing• Polyhydramnios• Hepatosplenomegaly• Oligohydramnios• Lymphadenopathy• Placental thickening Open table in a new tab Serum antibody levels may be measured to determine whether a woman suspected of CMV infection has a primary infection during pregnancy. A high level of maternal serum CMV IgG antibodies (higher than 2.0), together with a low level of CMV IgM antibodies (lower than 0.80), indicates that antibodies are present from a past infection. Either a low level of CMV IgG antibodies or a fourfold rise in IgG titers together with high level of CMV IgM antibodies in the maternal serum (higher than 0.80) could indicate acute primary infection (Hammond, 1999Hammond D. CytoGam infusions at home.Journal of Intravenous Nursing. 1999; 22: 331-335PubMed Google Scholar; Inoue et al., 2001Inoue T. Matsumura N. Fukuoka M. Sagawa N. Fujii S. Severe congenital cytomegalovirus infection with fetal hydrops in a cytomegalovirus-seropositive healthy woman.European Journal of Obstetrics & Gynecology and Reproductive Biology. 2001; 95: 184-186Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar; Nelson and Demmler, 1997Nelson C.T. Demmler G.J. Cytomegalovirus infection in the pregnant mother, fetus, and newborn infant.Clinics in Perinatology. 1997; 24: 151-160PubMed Google Scholar). It has been thought that the greatest risk for symptomatic congenital CMV infection to the fetus occurs when the woman develops a primary infection during the first half of pregnancy (Nelson and Demmler, 1997Nelson C.T. Demmler G.J. Cytomegalovirus infection in the pregnant mother, fetus, and newborn infant.Clinics in Perinatology. 1997; 24: 151-160PubMed Google Scholar). The prognosis for newborns with symptoms is generally less favorable than for those newborns with asymptomatic infection (Alford et al., 1990Alford C.A. Stagno S. Pass R.F. Britt W.J. Congenital and perinatal cytomegalovirus infections.Reviews of Infectious Diseases. 1990; 12: S745-S753Crossref PubMed Scopus (299) Google Scholar). However, it is important to realize that developmental disabilities caused by subclinical infection may not be evident for months to years. Identifiable symptoms of CMV infection in the fetus and newborn are listed in Table 2 (Demmler, 1991Demmler G.J. Summary of a workshop on surveillance for congenital cytomegalovirus disease.Reviews of Infectious Diseases. 1991; 13: 315-329Crossref PubMed Scopus (430) Google Scholar; Inoue et al., 2001Inoue T. Matsumura N. Fukuoka M. Sagawa N. Fujii S. Severe congenital cytomegalovirus infection with fetal hydrops in a cytomegalovirus-seropositive healthy woman.European Journal of Obstetrics & Gynecology and Reproductive Biology. 2001; 95: 184-186Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar; Leung et al., 2000Leung T.F. Ng P.C. Fok T.F. Wong M.C.K. Wong W. Cheung K.L. Pneumocystis carinii pneumonia in an immunocompetent infant with congenital cytomegalovirus infection.Infection. 2000; 28: 184-186Crossref PubMed Scopus (8) Google Scholar; Mehta and Hartnoll, 2001Mehta N.M. Hartnoll G. Congenital CMV with callosal lipoma and agenesis.Pediatric Neurology. 2001; 24: 222-224Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar; Nelson and Demmler, 1997Nelson C.T. Demmler G.J. Cytomegalovirus infection in the pregnant mother, fetus, and newborn infant.Clinics in Perinatology. 1997; 24: 151-160PubMed Google Scholar; Noyola et al., 2001Noyola D.E. Demmler G.J. Nelson C.T. Griesser C. Williamson W.D. Atkins J.T. Early predictors of neurodevelopmental outcome in asymptomatic congenital cytomegalovirus infection.Journal of Pediatrics. 2001; 138: 325-331Abstract Full Text Full Text PDF PubMed Scopus (243) Google Scholar). Most infants who are symptomatic have serious sequelae, including mental retardation (70%), sensorineural hearing loss (50%), dental defects (30–40%), and vision deficits (20%) (Stamos and Rowley, 1994Stamos J. Rowley A. Timely diagnosis of congenital infection.Pediatric Clinics of North America. 1994; 41: 1017-1033PubMed Google Scholar). The presence of microcephaly or an abnormal finding on a cranial computed tomography scan may be the most predictive indicators of mental retardation and major motor disability (Boppana et al., 1997Boppana S.B. Fowler K.B. Vaid Y. Hedlund G. Stagno S. Britt W.J. Neuroradiographic findings in the newborn period and long-term outcome in children with symptomatic congenital cytomegalovirus infection.Pediatrics. 1997; 99: 409-414Crossref PubMed Scopus (212) Google Scholar; Nelson and Demmler, 1997Nelson C.T. Demmler G.J. Cytomegalovirus infection in the pregnant mother, fetus, and newborn infant.Clinics in Perinatology. 1997; 24: 151-160PubMed Google Scholar; Noyola et al., 2001Noyola D.E. Demmler G.J. Nelson C.T. Griesser C. Williamson W.D. Atkins J.T. Early predictors of neurodevelopmental outcome in asymptomatic congenital cytomegalovirus infection.Journal of Pediatrics. 2001; 138: 325-331Abstract Full Text Full Text PDF PubMed Scopus (243) Google Scholar). Chorioretinitis also is associated with a poor neurodevelopmental outcome (Nelson and Demmler, 1997Nelson C.T. Demmler G.J. Cytomegalovirus infection in the pregnant mother, fetus, and newborn infant.Clinics in Perinatology. 1997; 24: 151-160PubMed Google Scholar). Those children with symptoms that spare the neurologic system (such as petechiae, hepatosplenomegaly, jaundice, and thrombocytopenia) are more likely to have normal or near-normal intellectual and neurodevelopmental outcomes (Nelson and Demmler, 1997Nelson C.T. Demmler G.J. Cytomegalovirus infection in the pregnant mother, fetus, and newborn infant.Clinics in Perinatology. 1997; 24: 151-160PubMed Google Scholar).Table 2Symptoms of Cytomegalovirus Infection in the Fetus and Newborn• Intrauterine growth restriction• Periventricular malformations• Hydrocephalus• Cystic brain lesions• Agenesis of the corpus callosum• Hydrops• Chorioretinitis• Stillbirth• Hepatosplenomegaly• Microcephaly• Hepatitis with jaundice• Thrombocytopenia• Anemia• Petechiae• Sensorineural hearing loss Open table in a new tab Much like herpes simplex virus type 2, CMV is thought to lie dormant in host tissue indefinitely and is reactivated periodically, particularly during pregnancy (Alford et al., 1990Alford C.A. Stagno S. Pass R.F. Britt W.J. Congenital and perinatal cytomegalovirus infections.Reviews of Infectious Diseases. 1990; 12: S745-S753Crossref PubMed Scopus (299) Google Scholar; Sherwen et al., 1999Sherwen L.N. Scoloveno M.A. Weingarten C.T. Maternity nursing: Care of the childbearing family.3rd ed. Appleton & Lange, Stamford, CT1999Google Scholar). The rate of infection of the fetus resulting from a recurrent maternal infection ranges from 0.2–1.8% (Nelson and Demmler, 1997Nelson C.T. Demmler G.J. Cytomegalovirus infection in the pregnant mother, fetus, and newborn infant.Clinics in Perinatology. 1997; 24: 151-160PubMed Google Scholar; Stamos and Rowley, 1994Stamos J. Rowley A. Timely diagnosis of congenital infection.Pediatric Clinics of North America. 1994; 41: 1017-1033PubMed Google Scholar). However, because CMV infection is usually acquired before the childbearing years, transmission of the reactivated virus in utero is likely the most common cause of congenital infection (Demmler, 1991Demmler G.J. Summary of a workshop on surveillance for congenital cytomegalovirus disease.Reviews of Infectious Diseases. 1991; 13: 315-329Crossref PubMed Scopus (430) Google Scholar). Recurrent maternal CMV infection is less likely to lead to symptomatic congenital CMV syndrome at birth, presumably because of protection by the pregnant woman's CMV IgG antibodies, which can cross the placenta and block severe fetal infection (Alford et al., 1990Alford C.A. Stagno S. Pass R.F. Britt W.J. Congenital and perinatal cytomegalovirus infections.Reviews of Infectious Diseases. 1990; 12: S745-S753Crossref PubMed Scopus (299) Google Scholar; Nelson and Demmler, 1997Nelson C.T. Demmler G.J. Cytomegalovirus infection in the pregnant mother, fetus, and newborn infant.Clinics in Perinatology. 1997; 24: 151-160PubMed Google Scholar). In rare cases, recurrent maternal CMV infection can cause severe symptomatic CMV infection in the fetus, as evidenced by fetal hydrops and stillbirth in two subsequent pregnancies in an asymptomatic seropositive Japanese woman (Inoue et al., 2001Inoue T. Matsumura N. Fukuoka M. Sagawa N. Fujii S. Severe congenital cytomegalovirus infection with fetal hydrops in a cytomegalovirus-seropositive healthy woman.European Journal of Obstetrics & Gynecology and Reproductive Biology. 2001; 95: 184-186Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar). This suggests that maternal CMV IgG antibodies may not always offer protection against severe fetal CMV infection (Inoue et al., 2001Inoue T. Matsumura N. Fukuoka M. Sagawa N. Fujii S. Severe congenital cytomegalovirus infection with fetal hydrops in a cytomegalovirus-seropositive healthy woman.European Journal of Obstetrics & Gynecology and Reproductive Biology. 2001; 95: 184-186Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar). Infants with subclinical infections may present with hearing loss, cerebral palsy, learning disabilities, seizure disorders, and mental retardation in early childhood (Noyola et al., 2001Noyola D.E. Demmler G.J. Nelson C.T. Griesser C. Williamson W.D. Atkins J.T. Early predictors of neurodevelopmental outcome in asymptomatic congenital cytomegalovirus infection.Journal of Pediatrics. 2001; 138: 325-331Abstract Full Text Full Text PDF PubMed Scopus (243) Google Scholar). Inguinal hernias in boys and defects of tooth enamel also are late symptoms associated with congenital CMV infection (Alford et al., 1990Alford C.A. Stagno S. Pass R.F. Britt W.J. Congenital and perinatal cytomegalovirus infections.Reviews of Infectious Diseases. 1990; 12: S745-S753Crossref PubMed Scopus (299) Google Scholar). Children with congenital CMV infection remain chronically infected for years and have been found to excrete the virus in their urine for an average of 4 to 5 years. Counter to what might be expected, Noyola et al., 2000Noyola D.E. Demmler G.J. Williamson W.D. Griesser C. Sellers S. Llorente A. Cytomegalovirus urinary excretion and long term outcome in children with congenital cytomegal
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