Updated 2006-01-18 by Juliana Leite, MD

Original text 1999-06-21 Philippe Jeanty, MD, PhD & Sandra R Silva, MD

Synonym: Congenital cytomegalovirus 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.

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 live-born infants have symptomatic disease at the time of birth and later. Few cases may have isolated findings such as ascites.

Diagnosis: Cytomegalovirus infection as well as other congenital infections should be suspected whenever no immune hydrops is found. Other suggestive findings that may be present are intracranial calcifications and intracranial hemorrhage, microcephaly, brain atrophy, abnormal periventricular echogenicities, intraparenchymal foci, ventriculomegaly, intraventricular adhesions, periventricular pseudocysts, 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 (marked by decreased motion of the foramen ovale flap and thickening of the flap), signs of right-heart overload from the premature closure, ascites, hyperechoic bowel, intrauterine growth restriction, and oligohydramnios. Most features are found by ultrasound examinations, around 20 weeks’ gestation.
Whenever maternal infection is confirmed, culture and polymerase chain reaction testing of amniotic fluid (4) 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" pregnancy, after a 7-week interval between diagnosis of maternal infection and antenatal procedure (2). The diagnosis can also be made by histologic study of typical inclusion bodies in biopsy or autopsy specimens.
Focal sonographic periventricular pattern associated with mild ventriculomegaly, without any abnormalities of the cerebral and cerebellar organogenesis, nor 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.

Figure 1: Splenomegaly. No measurements necessary: this spleen extends almost to the anterior abdominal wall.

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.

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 > 15 mm, it is associated with an increase in abnormal neurological development.

Recurrence risk: Considering that viral infection confers immunity in the majority, there is just a small theoretical risk of reinfection in another pregnancy.

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 severely affected.

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