Synonym: Congenital cytomegalovirus (CMV) infection.
Definition: Fetal cytomegalovirus infection is a congenital disorder characterized by hydrops, ascites, ventriculomegaly, and other findings caused by transplacental transmission of cytomegalovirus to the fetus. The double-stranded DNA herpes group virus causes a mild infection or a mononucleosis-type illness in young, healthy adults; chronic disease in older adults; and mild to severe congenital infection.126,127
Etiology: Cytomegalovirus (a double-stranded DNA herpes group virus).
Incidence: Congenital cytomegalovirus infection occurs in 0.2% to 2.2% of deliveries. Intrauterine transmission of CMV takes place in approximately 40% of infections, and approximately 10% of liveborn infants have symptomatic disease at the time of birth and later. Few cases may have isolated findings such as ascites.126,127
Diagnosis: Cytomegalovirus infection as well as other congenital infections should be suspected whenever no immune hydrops is found. Suggestive findings that may be present are intracranial calcifications and intracranial hemorrhage, abnormal periventricular echogenicities, intraparenchymal foci, ventriculomegaly, microcephaly, ascites, hyperechoic bowel, intrauterine growth restriction, and oligohydramnios (Figure 20-50). In some cases, other findings can be present such as intraventricular adhesions, periventricular pseudocysts, brain atrophy sulcation and gyral abnormal patterns, hypoplastic corpus callosum, cerebellar and cisterna magna abnormalities, signs of striatal artery vasculopathy, splenomegaly, chorioretinitis (an echogenic lining to the vitreous body), occlusion of the foramen ovale, and signs of right-heart overload from the premature closure.128, 129, 130, and 131
Fetus infected with cytomegalovirus demonstrating a bilateral ventriculomegaly. (Image contributed by Fabrice Cuillier, MD)
Whenever maternal infection is confirmed, culture and polymerase chain reaction (PCR) testing of amniotic fluid129 and/or cordocentesis is required for serologic studies (search for fetal-specific IgM antibody), although it does not have 100% reliability. PCR on amniocentesis samples can be made after 21 weeks of pregnancy, after a 7-week interval between diagnosis of maternal infection and antenatal procedure. The diagnosis can also be made by histologic study of typical inclusion bodies in biopsy or autopsy specimens.132, 133, and 134
Focal sonographic periventricular pattern in association with mild ventriculomegaly, without any abnormalities of the cerebral and cerebellar organogenesis or cephalic biometry alteration in the third trimester of pregnancy, should be considered as a marker of encephalitis following CMV infection of the fetal brain. Fetal MRI is a useful adjunct in the evaluation of intrauterine infection with CMV.
Pathogenesis: The exact mode of transplacental passage is uncertain. The virus replicates in fetal tissues, producing inflammation, tissue necrosis, and organ dysfunction. Cytomegalovirus hepatitis in the neonate can present with an intense inflammatory response involving the portal triads. In these cases, lobular disarray, degeneration of hepatocytes, and cholestasis are also seen. The cause of ascites in congenital cytomegalovirus infection is not certain. Contributing factors may include low serum protein levels due to hepatic dysfunction and portal obstruction resulting from periportal inflammation.
Associated Anomalies: Isolated ascites is an uncommon finding in fetuses with cytomegalovirus infection but may occur. Cardiovascular, gastrointestinal, musculoskeletal, and ocular lesions may be found in association with the classic features. Petechiae, neurosensory hearing loss, and poor intellectual development may also occur after birth.
Key Points: Intracranial calcifications, ventriculomegaly, microcephaly, ascites, hyperechoic bowel, intrauterine growth restriction, and oligohydramnios.
Differential Diagnosis: Because ascites is often the first manifestation of hydrops, the differential diagnosis for fetal ascites is essentially the same as with generalized hydrops, which includes mainly all congenital infections. Conditions that present intracranial calcifications (such as tuberous sclerosis), hyperechoic bowel (cystic fibrosis and Down syndrome), and hepatomegaly (primary liver disease or extramedullary hematopoiesis) should be considered.
Prognosis: In general, neonates with symptomatic cytomegalovirus infection do poorly, with a neonatal mortality rate as high as 30% and a high rate of neurologic handicap in survivors. Cytomegalovirus hepatitis is reversible in survivors, but mental retardation, motor handicaps, and hearing loss are expected long-term sequels. Late sequelae such as sensorineural hearing loss and neurodevelopmental disorders occur in 10% to 15% of infants lacking symptoms at birth. Pediatric neurological morbidity is related to the degree of antenatal ventriculomegaly and, when it is greater than 15 mm, it is associated with an increase in abnormal neurological development.135
Recurrence Risk: The cytomegalovirus is a ubiquitous virus that belongs to the herpes virus group. Intrauterine transmission may be caused by either primary or recurrent maternal infection. It seems that recurrent infection is more frequent than primary infection, but is considered less dangerous for the fetus.133,134
Management: Termination of pregnancy can be offered before viability. If continuation of the pregnancy is chosen, monthly follow-up with ultrasound is recommended to monitor growth restriction, hydrops, and the other fetal manifestations. Decompression with paracentesis to remove fetal ascites may prevent pulmonary hypoplasia and improve the circulatory system in those cases that are severely affected. Some authors described the treatment of fetuses infected with cytomegalovirus using maternal oral administration of valaciclovir (8 g/d). The results are still inconclusive.136
Prevention: Of all the ways to fight congenital CMV disease, the development of a vaccine is viewed as the most promising, but it is uncertain when a vaccine will become available. The American College of Obstetricians and Gynecologists guidelines recommend that physicians counsel pregnant women about preventing CMV acquisition through careful attention to hygiene.137