Recommendations of the Polish Society of Gynaecologists and Obstetricians and the Polish Society of Epidemiologists and Doctors of Infectious Diseases for screening, diagnosis and management of cytomegalovirus infection in pregnancy and congenital CMV infection.

Cytomegalovirus Infection in Pregnancy

Congenital cytomegalovirus (CMV) is the most common intrauterine infection and the leading infectious cause of sensorineural hearing loss and mental retardation. This article reviews the issues that relate to the diagnosis and management of this disease, detailing the points that led to the recent published guidelines by the Society of Obstetricians and Gynaecologists of Canada. A MEDLINE/Cochrane search of CMV infection, pregnancy, and prenatal diagnosis found 195 studies between 1980 and 2010. Of these, we examined 59 relevant studies. The probability of intrauterine transmission following primary infection is 30% to 40%, but only 1% after secondary infection. About 10% to 15% of congenitally infected infants will have symptoms at birth, and 20% to 30% of them will die, whereas 5% to 15% of the asymptomatic infected neonates will develop sequelae later. Children with congenital CMV infection following first trimester infection are more likely to have central nervous system sequelae, whereas infection acquired in the third trimester has a high rate of intrauterine transmission but a favorable outcome. The prenatal diagnosis of fetal CMV infection should be based on amniocentesis performed 7 weeks after the presumed time of infection and after 21 weeks of gestation. Sonographic findings often imply poor prognosis, but their absence does not guarantee a normal outcome. The value of quantitative determination of CMV DNA in the amniotic fluid is not yet confirmed. The effectiveness of prenatal therapy for fetal CMV is not yet proven, although CMV-specific hyperimmune globulin may be beneficial. Routine serologic screening of pregnant women or newborns has never been recommended by any public health authority. Obstetricians & Gynecologists, Family Physicians. After completion of this educational activity, the obstetrician/gynecologist should be better able to evaluate the principles of prenatal diagnosis of congenital CMV infection so doctors will be familiar with the tests and procedures needed, in order to reach a diagnosis of congenital CMV; to assess the natural history and outcome of congenital CMV infection enabling obstetricians to counsel prenatally pregnant women with CMV; and to analyze the prognostic markers for fetal CMV, so managing physicians will be able to predict more accurately the outcomes of fetuses infected by CMV.

Cytomegalovirus Infection

Screening for congenital cytomegalovirus infection: A tapestry of controversies

IN THIS ISSUE OF JAMA, BOPPANA AND COLLEAGUES 1 DEscribe their attempts to validate universal screening methods for congenital cytomegalovirus (CMV) infection, the most common congenital viral infection in the United States and many other regions, by using polymerase chain reaction (PCR) analysis of newborn dried blood spots. Congenital CMV infection remains an important public health problem not only because it has accounted for as much or more disability over the past 50 years than was associated with congenital rubella syndrome, but also because CMV infection, whether symptomatic or silent at birth, represents the most common nongenetic cause of permanent hearing loss among children in the United States. Congenital CMV infection causes a substantial proportion of sensorineural hearing loss even in regions with a low prevalence. Culture surveillance of nearly 4000 newborns in Utah revealed a congenital infection rate of 0.29%, corresponding to approximately 3 infected infants for every 1000 newborns or 165 infected newborns annually statewide, given the state’s current birth rate. Because as many as 10% of these infants will have CMV disease, a condition associated with a 30% to 50% prevalence of sensorineural hearing loss, and the remainder will have silent CMV infection, a condition conservatively associated with a 6% to 8% rate of sensorineural hearing loss, CMV accounts for hearing loss in 15 to 20 children each year in Utah, or approximately 20% of the 90 to 120 Utah children identified with permanent hearing loss annually (J. C. Carey, University of Utah School of Medicine, written communication, March 2010). Worldwide, thousands of infants have CMV-induced hearing loss annually. Universal newborn screening for many disorders has immense public health benefits. The history of phenylketonuria (PKU) illustrates the enormous benefit of such strategies. Universal screening of newborn hearing has led to improvement in language outcomes, with greater improvements when deaf infants are identified earlier and interventions are begun sooner. Thus, it seems logical to infer that if CMV-infected infants can be identified in the neonatal period, hearing could be tracked closely, interventions could begin early, and the hearing outcomes of congenital CMV infection might be improved. However, 2 challenges confront universal screening for congenital CMV infection. First, universal screening is only justified when an effective intervention exists that prevents adverse health outcomes, such as averting intellectual disability when infants who lack phenylalanine hydroxylase initiate a diet low in phenylalanine early in life. At present, no such solution exists for CMV. Although neonatal ganciclovir therapy improves hearing outcomes in some infants, the benefits are not universal and the risk/benefit ratio of ganciclovir therapy in infants with silent congenital CMV infection has not been sufficiently well-established to recommend such therapy for all CMV-infected infants. Nonetheless, knowing which infants are infected with CMV has benefit through early identification of infants at risk of CMVinduced hearing loss and may have additional benefits in the future when new and more effective antiviral strategies become available. The second challenge, the one addressed by Boppana et al, is the availability of a highly sensitive and specific screening method. Neonatal screening of hearing alone is insufficient to detect all CMV-infected infants because most infants with congenital CMV infection have normal hearing in the neonatal period. Fowler et al demonstrated that nearly 20% of the children with hearing loss due to silent congenital CMV infection have delayed onset of sensorineural hearing loss. In addition, most infants with congenital hearing loss do not have CMV infection. In 1996, when Barbi et al demonstrated that newborn dried blood spots and PCR assays could be used to detect CMV DNA in the blood of congenitally infected infants, there was optimism that the opportunity for universal screening for CMV had arrived. However, the study by Barbi et al was not population-based and did not have a sufficient sample size to establish convincingly the sensitivity and specificity of mass screening of newborn dried blood spots. In contrast, the large, prospective study by Boppana et al shows that even though real-time PCR has excellent specificity (approaching 100%), the sensitivity of the PCR

Congenital cytomegalovirus (CMV) infection is the most common nongenetic cause of sensorineural hearing loss and a major cause of visual, intellectual, and neurodevelopmental impairment worldwide. The seroprevalence of CMV among women of childbearing age in developing countries reaches almost 100%, and the incidence of CMV infection in neonates is 1%–2%. Approximately 87% of the infected neonates are asymptomatic at birth and 13% of them have permanent sequelae. The burden of congenital malformations due to congenital CMV infection is higher than that due to Down syndrome, fetal alcohol syndrome, and spina bifida. Nevertheless, there is little knowledge regarding congenital CMV pathogenesis, diagnosis, treatment, and prevention. In this study, we report a case that showed sequential changes of fetal brain following CMV infection in pregnancy. Additionally, we reviewed the latest information on the diagnosis, treatment, and prevention of congenital CMV infection.

Cytomegalovirus (CMV) is the most common cause of perinatal viral infection, affecting 0.2-2.2% of all neonates, with variation among different study populations. It can cause serious long-term neurological sequelae, being the leading cause of non-genetic congenital hearing loss. The risk of congenital infection is highest after primary maternal infection, varying between 30-70% and depending on the gestational age at the time of infection. Although CMV can have serious neurodevelopmental consequences, in most developed countries current guidelines do not recommend routine screening for CMV in pregnancy, since current tests have a low predictive value for cases with serious adverse outcome and efficient therapeutic options are not standardized yet. In Romania there is a routine clinical practice to offer screening for most common causes of infections, including CMV, in the first trimester of pregnancy In these settings, this review summarizes the current methods of diagnosis and management of CMV infection in pregnancy.

Management of cytomegalovirus infection in pregnancy: is it time for valacyclovir?

Human Cytomegalovirus and Kidney Transplantation: A Clinician's Update

Treatment with valacyclovir during pregnancy for prevention of congenital cytomegalovirus infection: a real-life multicenter Italian observational study

Cytomegalovirus (CMV) is a DNA herpesvirus that is common worldwide. The two known main sources of primary CMV infection during pregnancy are through sexual activity and contact with young children. Primary infection occurs in approximately 1 to 4% of pregnancies, and is mostly asymptomatic in immunocompetent adults. However, primary infection may manifest as a mild mononucleosis or flu-like syndrome with persistent fever and fatigue. CMV can be transmitted from mother-to-child in utero, intrapartum, or during breastfeeding. Intrauterine transmission can lead to congenital CMV infection, a leading cause of permanent hearing and vision loss and neurological disability among children. Congenital CMV transmission rates are as high as 50% in women who acquire primary CMV infection during pregnancy, and less than 2% in women with nonprimary infection. There is no licensed CMV vaccine. Good hygiene practices and avoiding intimate contact with young children (e.g., kissing on the mouth and sharing utensils) have been suggested as an approach to prevent maternal primary CMV infection during pregnancy, but remains an unproven method of reducing the risk of congenital CMV infection. Approximately 1 in 10 infants who acquire CMV in utero will have clinical signs at birth, and an additional 10 to 15% will go on to develop late-onset sequelae. Antiviral treatment prenatally and postnatally has not proven effective at preventing congenital or postnatal CMV infection, and is not recommended for routine clinical care. However, antiviral treatment when initiated in the first month of life for symptomatic congenital CMV infection is recommended for improved neurodevelopmental and audiologic outcomes. Birth Defects Research 109:336-346, 2017. © 2017 Wiley Periodicals, Inc.

SEVERE ESOPHAGITIS IN A NEWBORN INFANT

The purpose of this review is to serve as an update on congenital cytomegalovirus (CMV) evaluation and management for obstetrician-gynecologists and to provide a framework for counseling birthing people at risk for or diagnosed with a primary CMV infection or reactivation or reinfection during pregnancy. A DNA virus, CMV is the most common congenital viral infection and the most common cause of nongenetic childhood hearing loss in the United States. The risk of congenital CMV infection from transplacental viral transfer depends on the gestational age at the time of maternal infection and whether the infection is primary or nonprimary. Although the risk of congenital CMV infection is lower with infection at earlier gestational ages, clinical sequelae are more severe with maternal infections earlier in gestation. At present, routine screening for maternal CMV infection is not recommended by U.S. guidelines. When maternal primary infection is confirmed in early pregnancy, emerging data support consideration of maternal antiviral therapy to prevent congenital CMV infection. When congenital CMV infection is confirmed, typically after an abnormal prenatal ultrasound result, there are more limited data on the utility of maternal antiviral therapy. Universal newborn screening for congenital CMV infection is not mandatory in most U.S. states at present. Newborns diagnosed with congenital CMV infection undergo an extensive evaluation to determine whether neurologic symptoms are present, which guides postnatal evaluation and management. In this review, we discuss the diagnosis and management of maternal CMV infection, the risk and diagnosis of congenital CMV infection, prevention and potential treatment of congenital CMV infection in utero, and neonatal congenital CMV infection diagnosis and management.

BackgroundIn utero Cytomegalovirus (CMV) vertical transmission occurs predominantly during primary maternal infection. There are no known non-invasive methods for diagnosis of fetal infection before delivery, however some risk factors have been suggested. We aimed to evaluate the association between maternal CMV urinary excretion and congenital CMV infection.MethodsA retrospective cohort study of all women who were diagnosed with primary CMV infection during pregnancy in a single university affiliated tertiary medical center, between 2012 and 2016. We examined congenital CMV infection and disease rates among infants born to women with and without CMV urinary excretion.ResultsOverall, 126 women were included, 77 in the positive urinary excretion group, and 49 in the negative urinary excretion group. There was no difference in maternal symptoms between the groups. We found no difference in congenital CMV infection and disease rates between infants born to women with and without urinary excretion of CMV (congenital infection rate 37.1% vs. 24.4%, p = 0.209, congenital disease rate of 18.2% vs. 22.4%, p = 0.648). Women with positive urinary CMV excretion had lower IgG avidity values (36.7% vs 54.6%, p = 0.007), with no additional difference in serology pattern. Compared to asymptomatic women, those with CMV related symptoms did not have significantly higher rates of urinary excretion of CMV (70% vs. 60.5%, p = 0.38) or congenital infection rates (40.7% vs. 31.2%, p = 0.48).ConclusionAmong infants of women with primary CMV infection in pregnancy, we did not find an association between urinary excretion of CMV and congenital CMV infection.

Clinical factor associated with congenital cytomegalovirus infection in pregnant women with non-primary infection.