Congenital cytomegalovirus infection

Each year, thousands of children are born with or develop permanent disabilities such as hearing loss, vision loss, motor and cognitive deficits from congenital CMV infection (cCMV). However, awareness of cCMV and its associated sequelae is very low in pregnant women and healthcare providers. Both targeted and universal approaches to screen newborns for CMV infection are now achievable due to recent scientific advances including the development of a rapid, high-throughput method for detecting CMV in saliva, the efficacy of antiviral treatment in symptomatic infants, and the demonstration of cost effectiveness of CMV screening. Future studies are needed to address gaps in our understanding on the role of non-primary maternal CMV infections, the evaluation of antiviral treatment in asymptomatic infants, and the implementation of prevention strategies for cCMV.     

Congenital cytomegalovirus infection among twin pairs

Objective: The purpose of this study was to describe the fetal/neonatal cytomegalovirus (CMV) status according to chorionicity and outcome in twin pregnancies diagnosed with CMV.

Methods: An opportunistic diagnosis of CMV infection was performed in a tertiary referral center. All cases diagnosed in twin pregnancies (2006–2011) were included. Prenatal diagnosis was performed by CMV-DNA in the amniotic fluid (AF) of both fetuses only on the evidence of sonographic findings in either one or both twins. Neonatal screening was selectively assessed in symptomatic newborns, preterm, and infants born to HIV-infected mothers. Congenital infection was considered in the presence of CMV-DNA in AF, fetal tissues or newborn urine within the first 2 weeks of life, and symptomatic disease with clinical findings at birth or autopsy.

Results: A total of six twin pregnancies with congenital CMV infection were diagnosed, five dichorionic and one monochorionic diamniotic. Only one sibling was infected among dichorionic pregnancies, two diagnosed prenatally, and three after birth. In the monochorionic pregnancy, the diagnosis was performed prenatally and the two fetuses were infected and severely damaged.

Conclusions: Congenital CMV infection in twins might be related, among other factors, to chorionicity, and in DC twins a non-concordant infection can be expected.     

Congenital and perinatal cytomegalovirus lung infection

Abstract

Background: Cytomegalovirus (CMV) pneumonitis may be severe, even lethal, following congenital infection or in premature infants with perinatal infection.

Objective: To review the epidemiological, pathogenetic, clinical and therapeutic features of prenatal and perinatal CMV lung diseases.

Methods: Evaluation of all published papers listed on PubMed describing CMV pneumonitis in infants.

Results: CMV is frequent and severe in immunosuppressed infants but infrequent in full-term neonates and occurs more frequently after perinatal than after congenital infection, particularly in premature infants. In premature infants, CMV infection is often protracted and causes a diffuse interstitial pneumonitis leading to fibrosis and bronchopulmonary dysplasia (BPD). Congenital CMV infection should also be considered in newborns with severe acute respiratory distress syndrome and refractory respiratory failure with progression to early chronic lung disease. The association between breast milk-transmitted CMV and development of cystic lung disease and Wilson–Mikity syndrome has also been reported. Data on the efficacy of antiviral therapy for infants with respiratory CMV diseases are lacking and only anecdotal case reports are available.

Conclusions: Persistent CMV infection appears to cause a diffuse necrotizing pneumonitis with fibrosis leading to BPD, in both immunocompromised or preterm infants and, less frequently in immunocompetent infants. The role of antiviral therapy remains to be elucidated.     

Congenital cytomegalovirus infection following primary maternal infection in the third trimester

Objective  To determine the effect of primary cytomegalovirus (CMV) infection in the third trimester on fetal outcome.
Design  Observational study.
Setting  Four perinatal departments in tertiary hospitals in Israel.
Population  Twenty-eight women with primary CMV infection acquired after 25 weeks of gestation.
Methods  Prenatal evaluation included amniocentesis and ultrasonographic examinations. Maternal infection was determined from seroconversion and presence of low avidity anti-CMV immunoglobulin G after 25 weeks of gestation. Fetal CMV infection was diagnosed from CMV isolated or CMV DNA amplified from the amniotic fluid. Neonatal infection was established from CMV presence in their urine or anti-CMV IgM was in their peripheral blood immediately after birth. All liveborn neonates underwent cerebral ultrasonography, hearing assessment, and psychomotor development evaluation. Infected neonates were followed up for a median of 36 months (range 6–36 months).
Main outcome measures  Intrauterine CMV infection and neonatal CMV disease throughout follow up.
Results  Vertical transmission of CMV was documented in 21 (75%) of the 28 pregnancies. None of the 20 live infected newborn had symptomatic congenital infection. One pregnancy was terminated at 34 weeks following evidence of prenatal infection. Most of the patients (75%) had CMV serology test due to clinical signs of CMV disease.
Conclusions  Although CMV infection during the third trimester of pregnancy is highly transmissible, sequelae were not found among infected offspring.     

Congenital cytomegalovirus infection: review of the epidemiology and outcome

Cytomegalovirus (CMV) is one of the most common viral causes of congenital infection. A future decision to lower its incidence by vaccination will depend on epidemiological conditions within a country and on the safety of the vaccine to be used, because a life vaccine may cause latency and subsequent reactivation that still may harm the fetus. The aim was to review the epidemiological studies published so far, with respect to factors that affect the incidence of congenital CMV infection, and factors that may influence its outcome, such as preexisting maternal immunity. The study included the data of 19 studies that were retrieved from a MEDLINE search during the period 1977 to 1997. The incidence of congenital CMV infection varied between 0.15% and 2.0% and seemed to correlate with the level of preexisting immunity in the population. Although preexisting maternal immunity was reported to strongly reduce transmission, the severity of congenital CMV infection (symptoms at birth and or sequelae later in life) was not significantly greater after virus transmission due to a primary infection of the mother as compared with recurrence or reinfection. The data indicate that preexisting immunity of the mother does not significantly mitigate the outcome of congenital infection. Moreover, life vaccines may bear a serious risk when transmittable to the fetus. TARGET AUDIENCE: Obstetricians and Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader will be able to describe the natural course of a CMV infection, to list the potential sequelae of a congenital CMV infection, to outline potential strategies to prevent transmission of CMV, and to summarize the diagnostic work up of a patient with a potential CMV infection.     

Congenital cytomegalovirus infection in 1 twin with a pericardial effusion: a case report

BACKGROUND: Congenital fetal damage related to cytomegalovirus (CMV) infection is largely attributable to maternal primary infection. Twin fetuses may react differently to the same maternal influences. CASE: A woman had a sonographically documented fetal pericardial effusion in 1 twin at 33 weeks of gestation. The workup for maternal infection and fetal structural anomaly was negative except for positive CMV Ige in the maternal serum Cesarean section was performed due to fetal distress. After delivery, CMV viral antigenemia was found in 1 twin with petechiae, thrombocytopenia, hepatosplenomegaly and ventriculomegaly. The other twin was not infected and in stable condition. CONCLUSION: Since twin fetuses simultaneously exposed to the same maternal influence had a completely different outcome, maternal factors play a limited role in influencing CMV transmission.     

Congenital cytomegalovirus infection in pregnancy: a case report of fetal death in a CMV-infected woman

Objectives The human cytomegalovirus (CMV) is universally distributed among human populations as one of the most common cause of congenital infection with an incidence of about 0.15–2.0% in developed countries. However, controversial data concerning intrauterine fetal death caused by CMV infection exist. Method A case report. Results In this case report we present a stillbirth in the 18th week of pregnancy, caused by a maternal serological and fetal histological congenital CMV infection. Conclusion Every attending physician and obstetrician should be aware of the possibility of a primary or even recurrent congenital CMV infection that could be a reason for sudden unknown congenital fetal death.     

妊娠期人巨细胞病毒感染对母儿的影响及诊治

人巨细胞病毒是引起胎儿、婴儿先天性病毒感染的最常见原因之一。宫内明确诊断胎儿受损存在困难,IgG抗体亲和力测定、羊水的病毒检测结合超声检查对诊断有帮助。应用人巨细胞病毒特异性高效免疫球蛋白进行宫内的预防治疗有一定作用。对于人巨细胞病毒血清学阳性孕妇分娩早产儿或低出生体重儿,母乳喂养可能对新生儿有不利影响。     

Vesicovaginal fistula associated with cytomegalovirus infection in an HIV-infected patient

BACKGROUND: Cytomegalovirus (CMV) can cause multisystem disease in human immunodeficiency virus (HIV)-infected patients. An association with a vesicovaginal fistula has not previously been reported. CASE: An HIV-infected African-American female presented with back pain, swelling and paralysis of her lower extremities and continuous leakage of urine. Fundoscopic examination was typical of CMV retinitis. Doppler and CT studies showed bilateral deep vein thrombosis and bilateral pulmonary emboli, respectively. Anticoagulant therapy was started, and a Greenfield filter was placed. An examination under anesthesia and cystoscopy showed extensive vulvar and rectal condylomata, a large, necrotic, anterior vaginal mass, and a large vesicovaginal fistula. All necrotic tissue was resected and the biopsies taken identified CMV cytopathic effect. CONCLUSION: Vesicovaginal fistula in an immunocompromised individual may be a local manifestation of systemic CMV disease.     

Congenital cytomegalovirus infection as a preventable complication of maternal transfusion. A case report

Transfusion-mediated cytomegalovirus (CMV) infection among neonates and nonpregnant, adult female surgical patients has been described thoroughly. A case of symptomatic congenital CMV infection developed after a maternal transfusion during pregnancy. It is estimated that 2.5-12.5% of individual blood units mediate CMV infection though inadvertent transfusion of CMV-infected leukocytes. The use of CMV-seronegative or deglycerolized blood may eliminate or considerably reduce the risk of transfusion-mediated primary CMV infection in pregnant women and their fetuses. CMV-seronegative or deglycerolized blood is used routinely in the case of CMV-susceptible neonates and immunocompromised individuals who require a transfusion. Whenever possible, CMV-seronegative or deglycerolized blood should be used for transfusions in pregnant women who are CMV seronegative or whose serologic status is unknown.     

Pre- and periconceptional primary cytomegalovirus infection: risk of vertical transmission and congenital disease

OBJECTIVE: To estimate the risk of congenital cytomegalovirus infection and disease following primary maternal infection around the time of conception compared with the risk during later stages of pregnancy. DESIGN: Cohort study between 1990 and 2003. SETTING: Germany. PARTICIPANTS: One hundred and sixty-six pregnant women with serologically confirmed primary cytomegalovirus infection and known outcome. METHODS: Timing of primary cytomegalovirus infection by analysing the kinetics of cytomegalovirus-specific IgG and IgM antibodies, the IgG avidity index and neutralising antibodies. MAIN OUTCOME MEASURE: Onset of maternal primary infection in relation to congenital infection and disease. RESULTS: Preconceptional (between eight and two weeks before onset of the last menstrual period) was determined in three women and did not lead to congenital infection. Periconceptional infection (between one week before and five weeks after last menstrual period) occurred in 20 women with congenital infection in nine cases (45%). Timing was less precise (between eight weeks before and five weeks after last menstrual period) in an additional 10 women, three cases of which resulted in congenital infection. Of the 12 pregnancies in which congenital infection occurred, seven were terminated, six before the 12th week of gestation (WG 12) and one at WG 19 due to fetal hyperechogenic bowel. One of the five infected live-born infants delivered to a mother with periconceptional infection showed dystrophy and mild microcephaly at birth, but had a rather normal development at two years of age. Primary infections occurring between WG 6-20 and WG 20-38 resulted in transmission rates of 30% (27/89) and 58% (18/31), respectively. CONCLUSIONS: Counselling of women with periconceptional primary cytomegalovirus infection should be adjusted to offer prenatal diagnosis and high-level ultrasound controls due to the considerable risk for fetal infection and uncertainty of clinical outcome and disease.     

Placental morphology in cytomegalovirus infection

Three groups of placentae from 27 cases of cytomegalovirus infection were examined morphologically and by specific immunofluorescence. Placentae in Group 1 (four cases) had a mean gestational age of 24.5 +/- 2.5 weeks; those in Group 2 (11 cases) had a mean gestational age of 36.4 +/- 2.7 weeks; those in Group 3 (12 cases) had a mean gestational age of 40 +/- 1.8 weeks. A tendency towards increased placental weight was observed. In 23 cases, a haematogenous placentitis was suspected on gross examination. Some specific features were detected on light microscopy. In Group 1 the lesions were represented by pronounced dysmaturity of villous structures, diffuse reparative villitis and intervillitis allied to an abundance of cytomegalic cells and areas of necrosis and calcification. In Group 2 a chronic active process was indicated by the presence of vascular involvement, proliferative-necrotic and reparative villitis and fresh villous necrosis; cytomegalic cells were scarce. In Group 3 placentae there was a predominance of villous plate lesions similar to those found in the septicaemic phase of maternal infections; necrotizing, proliferative and, rarely, reparative villitis was present; cytomegalic cells were rare. We may conclude that placental morphology needs to be substantiated by special laboratory techniques for the detection of cytomegalovirus infection.     

Fetal cytomegalovirus infection: a case report

Congenital cytomegalovirus infection is the most common perinatal infection. We describe a case of primary maternal cytomegalovirus infection during pregnancy and the prenatal diagnosis of fetal cytomegalovirus infection. Diagnosis was accomplished with percutaneous umbilical blood sampling. The fetal blood was evaluated with viral cultures, cytomegalovirus serologic testing, and nonspecific indicators of infection. Amniotic fluid was also cultured. All cultures were positive, which confirmed fetal infection. The pregnancy was terminated. Autopsy findings were consistent with fetal infection. The significance and utility of prenatal diagnosis are discussed.     

Predicting congenital cytomegalovirus infection: Guerra et al

The article below summarizes a roundtable discussion of a study published in this issue of the Journal in light of its methodology, relevance to practice, and implications for future research. Article discussed: Guerra B, Simonazzi G, Puccetti C, et al. Ultrasound prediction of symptomatic congenital cytomegalovirus infection. Am J Obstet Gynecol 2008;198:380.e1-380.e7. The full discussion appears at www.AJOG.org, page e1-e3.