Prevalence: Human cytomegalovirus (CMV) is one of the most common causes of congenital infections in newborns, with an incidence varying from 0.2 to 2% of all live births. CMV represents the most common cause of intra-uterine infection. It is estimated that approximatively, half of pregnant woman are seronegative at the beginning of the pregnancy. But 1% of these, will develop primary infection during pregnancy. The prevalence of primary infection during pregnancy is between 0,7-4% according to social-economic status. The transmission to the fetus occurs in 1/3%. 10 % of the infected fetuses will be affected at birth, showing major signs of neonatal infection. On the remaining 90% who are asymptomatic at birth, 10 to 15% will have impaired development with hearing loss, mental retardation. Those affected babies develop congenital cytomegalovirus inclusion disease with a 20-30 % mortality rate and most survivors suffer severe neurological sequelae. The primary cytomegalovirus infection is usually subclinical in more than 90% of pregnant woman. When symptomatic, the disease is mostly similar to a mononucleosis syndrome.
Etiology: The cytomegalovirus is a ubiquitous virus which belongs to the herpes virus group. Intra-uterine 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.
Pathogenesis: Like other herpes virus, cytomegalovirus persists in the body and recurrent infections can occur throughout gestation. According to previous reports, no studies have proved that it is more dangerous when acquired early in gestation. The three mechanisms for recurrent infections:
-
reactivation of a latent virus (most commom one);
-
low grade chronic infection;
-
or less frequently reinfection with a different strain.
Recurrent infection is always asymptomatic. Cytomegalovirus reactivation or reinfection is defined as IgG antibodies titre increasing by four, with or without IgM antibodies presence. Recurrent infection is more frequent than primary infection during pregnancy and appears as in between 0.7 and 13% of seropositive pregnant women, according to socioeconomic status. Only 0.15 to 1.5% of recurrent infections are transmitted to the fetus. Maternal immunity may reduce the virulence of infections without suppressing any fetal injury although serious damage is rare after recurrent infection. Few reports describe severe fetal damage after recurrent infection. Clinically, apparent disease occurs in less than 5% of infected children following recurrent maternal infection, usually with hearing loss or chorioretinitis.
Ultrasound Findings: In utero, cytomegalovirus infection is a major cause of serious neurological sequelae in newborn infant. The signs of infection can be detected by scan examination and include: IUGR: Hydrops fetalis: Intracranial abnormalities: Microcephaly; Ventriculomegaly; Periventricular calcifications; Abnormal cerebral gyrations; Intra-abdominal calcifications and echogenic bowels: Splenomegaly: is often found in newborns with a congenital infection. Hepatomegaly: Hemolytic anemia; thrombocytopenic purpura
Implications for targeted examinations: When intra-abdominal calcifications are detected, viral tests and a karyotype must be performed (CMV, Herpes, Parvovirus B19).
Differential Diagnosis: When isolated spleen calcifications are detected, other viral etiologies must be seek (Parvovirus, Herpes). Many cases are in fact idiopathic. Prognosis: Antenatal infection with cytomegalovirus is detected either accidentally, when maternal blood is examined or in a routine scan, when severe of mild signs of fetal infections are found. Only 5% to 19% of all infected fetuses will show antenatal ultrasound findings.
Management: Most authors as in France do not recommended maternal serologic screening during pregnancy in spite of the high frequency of cytomegalovirus infections. In fact, prenatal diagnosis is usually proposed when maternal seroconversion is diagnosed or when ultrasound findings like IUGR, periventricular calcification, cerebellar ventriculomegaly, hyperechogenic fetal bowels or abdominal calcification are seen.
References:
1- Achiron R., Pinhas-hamiel O., Lipitz S., Heiman Z., reichman B., mashiach S.- Prenatal ultrasonographic diagnosis of fetal cerebral ventriculitis associated witha symptomatic maternal cytomegaloviurs infection. Prenatl Diagn 1994 ; 14 : 523-6.
2- Boumahni B., Randrianaivo H., Laffitte A., Kauffmann E., Barau G., Foourmaintraux A.- Maladie des incusions cytomégaliques sévères chez le fœtus d’une femmeimmunisée avant la grossesse. J Gynecol Obstet Biol Reprod 2003 ; 32 : 745-7.
3- Chaoui R., Zodan-Marin T., Wisser J.- Marked splenomegaly in fetal cytomegalovirus infection : detection suported by three dimensional power Doppler ultrasound. Ultrasound Obstet Gynecol2002 ; 20 : 299-302.
4- Rousseau T., Douvier S., Reynaud I., laurent N., Bour J.B., Durand C., Spagnolo G., sagot P.- Severe maternal cytomegalic inclusion disease after documented maternal reactivation of CMV infection during pregnancy. Prenatal diagn 2000 ; 20 : 333-6.
5- Watt-Morse M.L., Laifer S.A.,Hill L.M.- The natural history of fetal cytomegalovirus infection as assessed by serial ultrasound and fetal blood sampling : a case report. Prenatal Diagn 1995 ; 15 : 567-70.