Prenatal diagnosis of congenital human cytomegalovirus infection

Fifteen fetuses at risk of congenital human cytomegalovirus (HCMV) infection underwent prenatal diagnosis at 16–30 weeks' gestation by a combination of amniocentesis and fetal blood sampling. HCMV was isolated from the amniotic fluid in six patients, but HCMV-specific IgM was detected in only three of them. Two of the nine neonates, who were delivered following a negative prenatal diagnosis, had congenital HCMV infection diagnosed by virus isolation in the urine. The interval from infection to prenatal testing was 3 and 4 weeks in the two false-negative cases and ⩾ 7 weeks in the true-positive cases. Although timely testing for HCMV infection allows the option of termination of pregnancy, it may be flawed by false-negative results.     

Prenatal diagnosis of congenital cytomegalovirus infection in 189 pregnancies with known outcome

An Erratum has been published for this article in Prenatal Diagnosis 21(7) 2001, 605. Prenatal diagnosis (PD) of fetal cytomegalovirus (CMV) infection was performed in 242 pregnancies, with known outcome in 189 cases. In 141/189 pregnancies, PD was carried out on account of suspicious maternal CMV serology up to gestational week (WG) 23, and in 48 cases on account of abnormal ultrasonic findings detected between WG 18 and 39. Chorionic villus samples (n=6), amniotic fluid (AF, n=176) and/or fetal blood specimens (n=80) were investigated for detection of virus by cell culture, shell vial assay, PCR and/or CMV-specific IgM antibodies. Of 189 fetuses correctly evaluated by CMV detection either in fetal tissue following therapeutic abortion/stillbirth (n=24) or in urine of neonates within the first 2 weeks of life (n=33), 57 were congenitally infected. In women with proven or suspected primary infection, the intrauterine transmission rates were 20.6% (7/34) and 24.4% (10/41), respectively. Of the congenitally infected live-born infants, 57.6% (19/33) had symptoms of varying degree. The overall sensitivity of PD in the serologic and ultrasound risk groups was 89.5% (51/57). A sensitivity of 100% was achieved by combining detection of CMV-DNA and CMV-specific IgM in fetal blood or by combined testing of AF and fetal blood for CMV-DNA or IgM antibodies. There was no instance of intrauterine death following the invasive procedure. The predictive value of PD for fetal infection was 95.7% (132/138) for negative results and 100% (51/51) for positive results. Correct results for congenital CMV infection by testing AF samples can be expected with samples obtained after WG 21 and after a time interval of at least 6 weeks between first diagnosis of maternal infection and PD. In case of negative findings in AF or fetal blood and the absence of ultrasound abnormalities at WG 22–23, fetal infection and neonatal disease could be excluded with high confidence. Positive findings for CMV infection in AF and/or fetal blood in combination with CMV suspicious ultrasound abnormalities predicted a high risk of cytomegalic inclusion disease (CID). Furthermore, detection of specific IgM antibodies in fetal blood was significantly correlated with severe outcome for the fetus or the newborn (p=0.0224). However, normal ultrasound of infected fetuses at WG 22–23 can neither completely exclude an abnormal ultrasound at a later WG and the birth of a severely damaged child nor the birth of neonates which are afflicted by single manifestations at birth or later and of the kind which are not detectable by currently available ultrasonographic techniques. Copyright © 2001 John Wiley & Sons, Ltd.     

Is fetal gender a risk factor for severe congenital cytomegalovirus infection?

Cytomegalovirus is the main cause of congenital viral infection and amniotic fluid viral load appears to be the single nonclinical prognostic factor. However, as in other infectious diseases, host genetics may influence the severity of the disease. To test this hypothesis, we looked retrospectively at the fetal gender in cases of severe congenital cytomegalovirus infection in our database. We also analyzed the international English literature covering this subject between 1985 and 2003. The proportion of females with brain abnormalities was statistically different from that of males (62/258: 24% vs 30/251: 12%, p = 0.004). The risk of abnormal brain development in infected fetuses was twice as high in females than in males (Chi² = 8.7; OR = 2, IC [1.26–3.21]). In our cases, amniotic fluid CMV DNA load was not significantly higher in males than in females (p = 0.06) and was also similar in severely and non-severely infected fetuses (p = 0.09). Copyright © 2005 John Wiley & Sons, Ltd.     

Prenatal diagnosis of congenital cytomegalovirus infection: False-negative amniocentesis at 20 weeks' gestation

Cytomegalovirus (CMV) is the most common cause of congenital infection. Recent studies show amniocentesis to be a 100 per cent sensitive and 100 per cent specific predictor of congenital infection, and recommend that it be offered in the at-risk pregnancy. However, these publications have focused on pregnancies at or beyond 22 weeks' gestation. Here, we report a case of maternal CMV hepatitis at 7–8 weeks' gestation, in which culture and polymerase chain reaction testing for CMV in amniotic fluid at 20 weeks' gestation were negative, but the infant had a positive CMV urine culture shortly after delivery. Implications for the prenatal diagnosis of CMV infection are discussed.     

Accuracy of amniotic fluid testing before 21 weeks' gestation in prenatal diagnosis of congenital cytomegalovirus infection

Cytomegalovirus (CMV) is the most common cause of intrauterine infection. Recent publications show amniocentesis to have an 81–100 per cent sensitivity in antenatal diagnosis after 21 weeks' gestation. Testing before 21 weeks' gestation is less well documented. We performed 36 amniocenteses between 14 and 20 weeks' gestation. The sensitivity was 45 per cent and the specificity 100 per cent. Implications and possible causes of this low sensitivity are discussed.     

Intraventricular haemorrhage in a fetus with cerebral cytomegalovirus infection

Cytomegalovirus (CMV) is the leading infectious cause of prenatal neurological damage, which is particularly severe when primary maternal infection occurs during the first 16 weeks of gestation, at the time of organ development and neuronal migration. Vascular involvement has been suggested to be among thepossible pathogenic mechanisms of virus-induced pathology, in addition to direct viral effects. We report on a fetus with cerebral CMV infection, which had intraventricular haemorrhage, together with oligohydramnios and hyperechogenic bowel, following maternal primary CMV infection. Copyright © 2002 John Wiley & Sons, Ltd.     

Identification and management of congenital parvovirus B19 infection

Parvovirus B19 (B19V) infection is well known for its mild, self-limiting clinical presentations in children, such as erythema infectiosum. Approximately 40% of women of childbearing age are susceptible to B19V infection. While maternal B19V infection usually has a good prognosis, B19V can cause severe fetal anaemia and pregnancy loss due to its ability to suppress erythroid progenitor cells. Non-invasive ultrasound monitoring for fetal anaemia is usually performed if maternal seroconversion occurs in the first 20 weeks of gestation, with amniocentesis for fetal infection reserved for those who first present with fetal anaemia or hydrops of unknown cause. Intrauterine transfusion is the standard treatment for severe fetal anaemia and is associated with a significant improvement in survival. However, survivors of hydrops fetalis may have a higher rate of long-term neurodevelopmental complications compared with non-hydropic survivors. This review aims to synthesise published data on the diagnosis, surveillance and outcomes of congenital parvovirus infection to assist clinicians in diagnosing and managing this important condition.     

Prenatal diagnosis of cytomegalovirus (CMV) infection: A preliminary report

Eight patients were referred for prenatal diagnosis for suspected fetal cytomegalovirus infection (CMV): six for documented first-trimester infection and two for abnormal ultrasound evaluation suggestive of fetal infection. Three methods of diagnosis were employed: (1) amniotic fluid viral cultures and CMV-specific IgM in fetal serum; (2) amniotic fluid cultures and detection by polymerase chain reaction amplification of CMV-specific DNA in chorionic villi; and (3) detection of CMV-specific DNA in villus samples only. Amniotic fluid cultures detected all cases of infection, but CMV-specific IgM was not a reliable indicator of infection in any case. DNA analysis correlated well with both culture results and clinical outcome.     

Prenatal ultrasonographic diagnosis of fetal cerebral ventriculitis associated with asymptomatic maternal cytomegalovirus infection

Cytomegalovirus is the most common cause of congenital viral infection. In utero infection is usually suspected in patients with growth-retarded fetuses or when maternal illness precipitates serological investigations. A case is presented where routine ultrasound examination at 30 weeks' gestation in an asymptomatic patient demonstrated mild fetal ventriculomegaly. Transvaginal ultrasound enabled the visualization of intraventricular adhesions and small periventricular cysts. The suspected diagnosis of in utero cytomegalovirus infection was confirmed by the presence of IgM antibodies in fetal blood and subsequently by isolation of the virus from the infant's urine. The presence of mild fetal ventriculomegaly should prompt transvaginal brain imaging.     

Brain cortical assessment by MRI in fetuses with left congenital diaphragmatic hernia

Objective

To evaluate fetal brain development using MRI (magnetic resonance imaging) in CDH (congenital diaphragmatic hernia).

Methods

52 isolated left CDH and 104 control fetuses were imaged using MRI. Brain morphometry (Biparietal diameter—BPD, brain fronto-occipital diameter—BFOD, third ventricle, posterior ventricles, transcerebellar diameter—TCD, anteroposterior and craniocaudal cerebellar vermis diameter—AP and CC) and cortical structures (bilateral cingulate fissure—CF, insular fissure—IF, insular depth - ID) were compared with controls using Mann–Whitney test.

Results

Median gestational age at MRI (p = 0.95)and the median biparietal diameter (p = 0.737) were comparable. Among morphometric parameters, only the brain fronto-occipital diameter was significantly smaller in CDH (p = 0.001) and the third ventricle was significantly greater in CDH (<0.0001). Among cortical structures, the cingulate and insular fissures were significantly deeper in CDH fetuses (p < 0.0001) as the insular depth ID was smaller in CDH (p < 0.03).

Conclusions

CDH fetuses have a smaller fronto-occipital diameter, reduced insular depth, deeper cingulate and insular fissure, and greater third ventricle width as compared to controls. These findings suggest that left CDH may have an impact on fetal brain development with an overall reduction in brain volume.