2006-09-19-09 Cytomegalovirus infection © Cuillier www.thefetus.net/
Cuillier F, MD*, Lai JH, MD**, SIboud M, MD***
* Department of Gynecology, Félix Guyon’Hospital ** Department of Gynecology, Saint-Benois’Hospital *** Department of neonatology, Félix Guyon’Hospital, 97400 Saint-Denis, Ile de la Réunion, France.
Definition: Cytomegalovirus can be responsible for severe fetal infection by maternal prime-infection. Nevertheless, even previously immunized woman, can have another infection, which are usually less important and severe to the fetus. We presented one case of cytomegalovirus fetal infection. The ultrasound examination at 32 weeks revealed few spleen and perigastric calcifications. The patient was previously immunized against the virus. Recent publications have reported similar observations with variable viral strains. These findings point out the importance attentive search for ultrasonographic signs, suggestive of cytomegalovirus infection, even for immunized woman.
Case Report: This is a G3P2 woman, referred at 32 weeks for the evaluation of spleen calcification. There was no intra-uterine growth restriction. Brain examination was strictly normal. Examination of the abdomen revealed an absence of fetal ascites, but few calcifications were seen inside the spleen and around the anterior wall of the stomach. The bowel was not hyperechoic. Echocardiogram was normal. Maternal blood sampling was performed. The results indicated asymptomatic old cytomegalovirus infection (IgG 2100 UI/ml and IgM = 0 UI/ml). The patient accepted to be a submitted to an amniocentesis (46XX), including polymerase chain reaction (PCR) search for viral contamination. There cytomegalovirus was not detected in the amniotic fluid. Because the patient was seronegative for toxoplasmosis, two maternal serum samples (one from more than three months before conception), had been tested for toxoplasmosis and were frozen. These sera were tested for CMV immunoglobulin by two different antibodies assays. The patient was already immunized. At 36 weeks, same anomalies remained the same.
At 39 weeks, a baby boy (3500 g) was delivered vaginally. Cytomegalovirus was isolated from the neonatal urine. Clinical examination revealed thrombocytopenia and a mild increase of liver enzymes. There was a hepatomegaly, but no splenomegaly. The neurological examination was normal. An abdominal scan did not find the calcifications. At day 5, the child was discharged from our hospital.
Finally, the mother infection was not confirmed by PCR although the mother has previously tested as immunized for cytomegalovirus at the beginning of the pregnancy. The baby had probably a cytomegalovirus infection due to a maternal reinfection.
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.
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