Cranial Ultrasound Scanning and Prediction of Outcome in Newborns with Congenital Cytomegalovirus Infection

doi:10.1016/j.jpeds.2006.11.032

The Journal of Pediatrics

Volume 150, Issue 2, February 2007, Pages 157-161

https://doi.org/10.1016/j.jpeds.2006.11.032 Get rights and content

Objective

To report the accuracy of ultrasound scanning (US) in predicting neurodevelopmental and sensorineural outcome in patients with congenital cytomegalovirus (CMV) infection.

Study design

Fifty-seven neonates with congenital CMV infection underwent brain US and were observed prospectively for motor skills, developmental quotient, and hearing function.

Results

Abnormal results on US were found in 12 of 57 neonates. US lesions were more frequent in newborns with clinical and laboratory signs of congenital CMV infection at birth (10/18) than in newborns who had no symptoms at birth (2/39; P < .001). At least 1 sequela developed in all neonates with symptoms who had abnormal US results, whereas none of the neonates with symptoms who had normal US results had long-term sequelae (P < .001). In the population without symptoms, sensorineural hearing loss developed in 3 of 37 (8.1%) neonates with normal US results, whereas severe sequelae developed in 1 of 2 neonates with abnormal US results.

Conclusions

A good correlation was found between cerebral US abnormalities and the prediction of outcome in newborns who were congenitally infected with CMV and had symptoms at birth. US could be performed as the first neuroimaging study in these newborns. Data are insufficient to permit any suggestions for the population without symptoms.

Section snippets

Methods

Between January 1997 and September 2003, 57 newborns in whom congenital CMV infection was diagnosed were referred to our tertiary care hospital, where we have set up a multidisciplinary team specializing in the treatment of patients with congenital CMV infection.

Congenital CMV infection was diagnosed on the basis of isolation of the virus from urine within the first 2 weeks of life in neonates born from mothers with a suspected or ascertained CMV infection during pregnancy.⁹ Virus isolation was

Results

Twelve of 57 (21.0%) neonates referred to our institution with a diagnosis of congenital CMV infection showed cerebral US abnormalities typical of congenital CMV infection. Eighteen of 57 (31.6%) showed clinical or laboratory signs of congenital infection at birth. US lesions were more frequent in newborns with clinical and laboratory signs of congenital CMV infection at birth (10/18) than in newborns who had no symptoms at birth (2/39; P = .000). Clinical data for patients with normal and

Discussion

CMV infection is the most common intrauterine infection in developed countries, with a prevalence of 0.2% to 2.2% in live neonates. Cerebral lesions, including meningoencephalitis, calcifications, microcephaly, disturbance of neuronal migration, germinal matrix cysts, ventriculomegaly and cerebellar hypoplasia, may develop in patients who are congenitally infected. The severity of the neuropathologic findings at birth correlates with poor outcome, including hearing loss, mental retardation,

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Viral infections of the fetus and newborn are common and frequently under recognized. Viral infections can be acquired in utero, intrapartum, or postpartum. The outcome of infection frequently depends on the timing of acquisition. The consequences of some infections can be evident at birth when infants present with symptoms such as intrauterine growth restriction, hepatitis, thrombocytopenia, and neurologic abnormalities. In other infections, the infant may be asymptomatic at birth but develop severe disease in the neonatal period. Timely and specific identification of viral infections is important as there are an increasing number of antiviral therapeutic agents available and appropriate treatment can be lifesaving. Identification of viral disease in the neonate may also provide important prognostic information, particularly for viruses associated with a high risk of neurodevelopmental issues. Accordingly, making a diagnosis of a viral infection can help to direct and focus long-term management. Fortunately, with the availability of molecular tools for specific viral detection using polymerase chain reaction (PCR) amplification of viral nucleic acid, virtually all pathogenic viruses can be rapidly identified. This chapter reviews the epidemiology, pathogenesis, diagnosis, clinical management, outcomes, and prevention of many common congenital and perinatal viral infections encountered in neonates.
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The infection due to cytomegalovirus is the most common congenital infection in developed countries, and on of the main causes of psychomotor impairment and neurosensory hearing loss of infectious origin.
The present study has its objectives to describe the clinical-analytical and neuroimaging of patients with secondary neurological sequelae secondary to the congenital cytomegalovirus infection and then compare them with the group of patients with a congenital cytomegalovirus infection that did not have neurological symptoms during their follow-up.
A retrospective, observational, cohort study was conducted that included all the cases of congenital cytomegalovirus infection from 2003 until 2018 and the short-medium term neurological sequelae were evaluated. Prenatal, perinatal, and postnatal data of patients with neurological sequelae were compared against those that did not present with any.
A total of 60 patients with congenital cytomegalovirus infection were recorded during the study period, with 65% having neurological involvement during their follow-up period (62.2% with psychomotor impairment, 61.5% with microcephaly, 46.2% loss of hearing, 27.8% motor disorders, 20.5% epilepsy, and 5.6% with chorioretinitis). In the patient group that had sequelae, the presence of clinical symptoms during the neonatal period, as well as changes in the neuroimaging study, were the most common, with both being statistically significant compared to the asymptomatic group. The patients with neurological involvement also had a higher score on the Noyola et al. neuroimaging scale.
The symptoms at birth, and certain findings in the neuroimaging, like the changes in the white matter or neuronal migration disorders, could predict neurocognitive sequelae in patients with congenital cytomegalovirus infection.
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Congenital cytomegalovirus (CMV) infection is the most common non-genetic cause of hearing loss and neurological disorder in children. Its overall prevalence is approximately 0.5% in Europe. In France, systematic screening during pregnancy is not recommended; screening is performed only if there are maternal or fetal symptoms suggestive of this infection. Approximately 90% of infected newborns are asymptomatic at birth, and among them the risk of neurosensory sequelae is 5–15%. By contrast, the prevalence of neurosensory impairment in symptomatic newborns at birth varies from 17% to 60%. Congenital CMV infection must be confirmed at birth before the 21st day of life by polymerase chain reaction (PCR) on saliva or urine samples. A complete clinical examination, blood tests (blood count, liver function test, CMV PCR), hearing tests, brain ultrasound and eye fundus examination should be performed. Neurological and auditory follow-up must be extended well beyond the neonatal period because the occurrence of neurosensory sequelae may be delayed. Oral valganciclovir is the recommended treatment in moderate or severe congenital CMV infections for a period of 6 weeks to 6 months; such treatment requires regular monitoring because of its possible side effects.
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L’infection congénitale à cytomégalovirus (CMV) est diagnostiquée soit pendant la vie fœtale sur des signes d’appel échographiques ou sur la notion d’une primo infection maternelle, soit devant une symptomatologie néonatale évocatrice. Les facteurs prédictifs de séquelles neurosensorielles sont l’âge gestationnel de la contamination fœtale, la présence de signes cliniques néonatals et les données de l’imagerie cérébrale ante et néonatale. Les séquelles neurosensorielles concernent 60 % des nouveau-nés symptomatiques et 15 % des asymptomatiques. Il s’agit, par ordre de fréquence, de déficit auditif, troubles vestibulaires, infirmité motrice, déficit visuel, déficit cognitif, troubles du comportement. La possibilité d’apparition secondaire d’un déficit auditif justifie la surveillance systématique des nouveau-nés infectés jusqu’à l’âge de 4 à 7 ans. Beaucoup d’inconnues persistent sur les indications et le bénéfice attendu du traitement antiviral par (val)ganciclovir.
Congenital cytomegalovirus (CMV) infection is diagnosed either antenatally on echographic presenting symptoms or on the background of primary infection in the mother, or in front of a suggestive neonatal symptomatology. Predictive factors for neurosensory sequelae include gestational age of fetal infection, whether neonatal clinical signs are present or not, and data from antenatal and neonatal brain imaging. Neurosensory sequelae occur in 60% of symptomatic and 15% of asymptomatic newborns. These include, in order of frequency, hearing impairment, vestibular disorders, visual impairment, cerebral palsy, cognitive impairment and autism spectrum disorders. The possibility of delayed onset hearing loss warrants prolonged monitoring of the children up to the age of 4 to 6 years. Many unknowns persist on the indications and expected benefit of antiviral treatment with Ganciclovir.
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Citation Excerpt :
Congenitally acquired cytomegalovirus infection can result in a wide range of brain lesions including polymicrogyria, pachygyria, diffuse white matter abnormality, ventriculomegaly, periventricular calcifications, temporal lobe cysts (Fig. 4.26), and cerebellar hypoplasia. Although fetal and postnatal MRI provides excellent detail of cortical migrational disorders and cerebellar abnormalities and can detect abnormal white matter as elevated signal intensity on T2-weighted imaging (Oosterom et al., 2015), cranial ultrasound is better for visualizing calcification (Ancora et al., 2007), lenticulostriate vasculopathy, and germinolytic cysts (de Vries et al., 2006). While fetal MRI has a low positive predictive value for later neurologic impairment, temporal or occipital cysts and migration disorders observed on fetal MRI were associated with sensory neural hearing loss and neurologic impairment (Cannie et al., 2016).
Magnetic resonance imaging (MRI) can provide detail of the soft tissues of the fetal and neonatal brain that cannot be obtained by any other imaging modality. Conventional T1 and T2 weighted sequences provide anatomic detail of the normally developing brain and can demonstrate lesions, including those associated with preterm birth, hypoxic ischemic encephalopathy, perinatal arterial stroke, infections, and congenital malformations. Specialized imaging techniques can be used to assess cerebral vasculature (magnetic resonance angiography and venography), cerebral metabolism (magnetic resonance spectroscopy), cerebral perfusion (arterial spin labeling), and function (functional MRI). A wealth of quantitative tools, most of which were originally developed for the adult brain, can be applied to study the developing brain in utero and postnatally including measures of tissue microstructure obtained from diffusion MRI, morphometric studies to measure whole brain and regional tissue volumes, and automated approaches to study cortical folding. In this chapter, we aim to describe different imaging approaches for the fetal and neonatal brain, and to discuss their use in a range of clinical applications.

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^⁎: Gina Ancora, MD and Marcello Lanari, MD, PhD contributed equally to this article.

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Original articleCranial Ultrasound Scanning and Prediction of Outcome in Newborns with Congenital Cytomegalovirus Infection

Objective

Study design

Results

Conclusions

Section snippets

Methods

Results

Discussion

J Pediatr

J Pediatr

J Pediatr

Pediatr Neurol

Early Hum Dev

J Pediatr

Brain Dev

Viral, protozoan, and related intracranial infections

Congenital cytomegalovirus infection of the brain: imaging analysis and embryologic considerations

AJNR Am J Neuroradiol

Neuroradiographic findings in the newborn period and long-term outcome in children with symptomatic congenital cytomegalovirus infection

Pediatrics

Fetal cytomegalovirus infection of the brain: the spectrum of sonographic findings

AJNR Am J Neuroradiol

The spectrum of cranial ultrasound and magnetic resonance imaging abnormalities in congenital cytomegalovirus infection

Neuropediatrics

Ganciclovir treatment of symptomatic congenital cytomegalovirus infection: results of a phase II study

J Infect Dis

Neonatal cytomegalovirus blood load and risk of sequelae in symptomatic and asymptomatic congenitally infected newborns

Pediatrics

Ventricular dilation after neonatal periventricular-intraventricular hemorrhage: natural history and therapeutic implications

Am J Dis Child

Original article
Cranial Ultrasound Scanning and Prediction of Outcome in Newborns with Congenital Cytomegalovirus Infection