Prenatal diagnosis of symptomatic congenital cytomegalovirus infection

doi:10.1067/mob.2000.106347

American Journal of Obstetrics and Gynecology

Volume 183, Issue 2, August 2000, Pages 476-482

https://doi.org/10.1067/mob.2000.106347 Get rights and content

Abstract

Objective: The aim of this study was to evaluate whether the amniotic viral load of mothers with primary cytomegalovirus infection correlate with fetal or neonatal outcomes. Study Design: Sixty-eight of 138 pregnant women with primary infection defined by immunoglobulin G seroconversion or the presence of immunoglobulin M with low immunoglobulin G avidity accepted amniocentesis. Polymerase chain reaction and quantitative polymerase chain reaction were used to detect amniotic fluid cytomegalovirus. Cytomegalovirus infection in neonates was determined by means of urinary viral isolation during the first week after birth or the histologic examination of tissue from aborted fetuses. Results: Cytomegalovirus infection was found in 16 fetuses and neonates (23%), 5 of whom had symptoms. Quantitative polymerase chain reaction showed that the presence of ≥10³ genome equivalents predicted mother-child infection with 100% probability; ≥10⁵ genome equivalents predicted the development of a symptomatic infection. Conclusion: Fewer than expected cytomegalovirus-infected fetuses are at risk for development of cytomegaloviral disease, and this fact may be useful in counseling pregnant women with primary cytomegalovirus infection. (Am J Obstet Gynecol 2000;183:476-82.)

Section snippets

Study population

In a number of Italian regions, pregnant women undergo routine CMV screening before the 12th week of gestation with commercially available kits for both anti–CMV immunoglobulin G (IgG) and anti–CMV immunoglobulin M (IgM). Seronegative women are reassessed after 16 to 18 weeks' gestation and during the third trimester. The women who have seroconversion and those who are IgM-seropositive are referred for further diagnostic evaluation.

During the last 5 years (1994-1998) 2 serum samples taken from

Results

With the exception of 5 patients in the third trimester amniocentesis was offered to all the women with primary infection (n = 138), 68 of whom (49.2%) followed our advice mainly in the hope of continuing the pregnancy with more confidence in the case of a negative result. In particular, amniocentesis was promptly accepted by 4 women with abnormal ultrasonographic findings to allow further investigation. The remaining 50.8% did not choose to undergo this procedure, mainly because we admitted

Comment

In this study the quantitative PCR determination of amniotic fluid viral load predicted both the infectious and the clinical outcomes of maternal CMV infection in fetuses and neonates. These findings may help clinicians to counsel pregnant women infected by CMV about the likely outcome for the offspring and enable the women themselves to decide the future of the pregnancy on a more informed basis.

The aim of prenatal diagnosis is to distinguish infected from uninfected fetuses, for which the

Acknowledgements

We thank Kevin Smart (LINK, Milan, Italy) for his help in preparing the manuscript.

References (25)

CS. Peckham
Cytomegalovirus infection: congenital and neonatal disease
Scand J Infect Suppl
(1991)
S Boppana et al.
Symptomatic congenital cytomegalovirus infection: neonatal and mortality
Pediatr Infect Dis J
(1992)
KB Fowler et al.
The outcome of congenital cytomegalovirus in relation to maternal antibody status
N Engl J Med
(1992)
Y. Ville
The megalovirus [editorial]
Ultrasound Obstet Gynecol
(1998)
MD. Yow
Congenital cytomegalovirus disease: a NOW problem
J Infect Dis
(1989)
CT Nelson et al.
Cytomegalovirus infection in the pregnant mother, fetus, and newborn infant
Clin Perinatol
(1997)
S Lipitz et al.
Prenatal diagnosis of fetal primary cytomegalovirus infection
Obstet Gynecol
(1997)
MG Revello et al.
Improved prenatal diagnosis of congenital human cytomegalovirus infection by a modified nested polymerase chain reaction
J Med Virol
(1998)
T Lazzarotto et al.
Prenatal diagnosis of congenital cytomegalovirus infection
J Clin Microbiol
(1998)
T Lazzarotto et al.
Anticytomegalovirus (anti-CMV) immunoglobulin G avidity in identification of pregnant women at risk of transmitting congenital CMV infection
Clin Diagn Lab Immunol
(1999)

T Lazzarotto et al.

Avidity of immunoglobulin G directed against human cytomegalovirus during primary and secondary infections in immunocompetent and immunocompromised subjects

Clin Diagn Lab Immunol

(1997)

L Grangeot-Keros et al.

Value of cytomegalovirus (CMV) IgG avidity index for the diagnosis of primary CMV infection in pregnant women

J Infect Dis

(1997)

Cited by (166)

Viral Infections of the Fetus and Newborn
2023, Avery's Diseases of the Newborn
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.
Neurological sequelae in patients with congenital cytomegalovirus
2020, Anales de Pediatria
La infección por citomegalovirus es la infección congénita más frecuente en los países desarrollados y una de las principales causas de retraso psicomotor y sordera neurosensorial de origen infeccioso.
El presente estudio tiene como objetivos describir las características clínico-analíticas y de neuroimagen de los pacientes con secuelas neurológicas secundarias a la infección congénita por citomegalovirus y compararlas con el grupo de pacientes con infección congénita por citomegalovirus que no presentaron clínica neurológica durante su seguimiento.
Estudio de cohortes retrospectivo, observacional. Se incluyeron todos los casos de infección congénita por citomegalovirus desde 2003 hasta 2018 y se evaluaron las secuelas neurológicas a corto-medio plazo. Se compararon datos prenatales, perinatales y posnatales de los pacientes con secuelas neurológicas frente a los que no las presentaron.
En el periodo descrito se registraron 60 pacientes con infección congénita por citomegalovirus: un 65% presentó afectación neurológica durante su periodo de seguimiento (retraso psicomotor 62,2%; microcefalia 61,5%, hipoacusia 46,2%; trastornos motores 27,8%; epilepsia 20,5% y coriorretinitis 5,6%). En el grupo de pacientes que presentó secuelas, la presencia de clínica en el periodo neonatal así como las alteraciones en el estudio de neuroimagen fueron más frecuentes y ambas fueron estadísticamente significativas respecto al grupo asintomático. Los pacientes con afectación neurológica también presentaron mayor puntuación en la escala de neuroimagen según Noyola et al.
La sintomatología al nacimiento y ciertos hallazgos en la neuroimagen, como la presencia de alteraciones de la sustancia blanca o trastornos de la migración neuronal, podrían predecir las secuelas neurocognitivas en los pacientes con infección congénita por citomegalovirus.
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.
Viral Infections and the Neonatal Brain
2019, Seminars in Pediatric Neurology
This review includes the congenital infections best known by the acronym TORCH (Toxoplasma gondii, rubella virus, cytomegalovirus, and herpes virus), as well as Zika virus infection and perinatally acquired infections (enterovirus, parechovirus, rotavirus, parvovirus). Congenital infections are due to pathogens that can cross the placenta and are more likely to injure the brain when the infection occurs early in pregnancy. There are many similarities, with regards to brain lesions, for congenital Zika syndrome and congenital cytomegalovirus infection. Perinatally acquired viral infections tend to injure the white matter, with cystic evolution being more likely in the (late) preterm infant compared to the full-term infant. Congenital and perinatally acquired viral infections can be associated with adverse neurological outcomes. Prevention is important, especially as therapeutic options are limited. In this review both congenital as well as perinatally acquired viral infections will be discussed with a focus on neuro-imaging findings.
Fetal Infections
2019, Fetal Medicine: Basic Science and Clinical Practice
Intraventricular haemorrhage as the first manifestation of congenital Cytomegalovirus infection
2018, Indian Journal of Medical Microbiology
Congenital Cytomegalovirus infection (CCMV) is the most common intrauterine infection. Early diagnosis of CCMV is hindered by three factors: There is no screening programme for CMV infection in pregnant women; a high percentage of infections in neonates are asymptomatic; the clinical signs of CCMV infection are uncharacteristic. The aim of this article is to analyse the clinical picture and course of CCMV treatment in a 3-week-old newborn, analyse adverse events in 14-week-long antiviral therapy and also assess intraventricular bleeding as an early indicator for the diagnosis of CCMV.
Congenital cytomegalovirus infection
2018, Seminars in Perinatology
Citation Excerpt :
Amniocentesis to perform PCR for CMV DNA in the amniotic fluid is the preferred diagnostic approach for identifying an infected fetus.50–53 Timing of amniocentesis is critical since the sensitivity for detection of CMV is higher after 21 weeks of gestation.50–52 If amniocentesis is performed earlier in gestation or soon after diagnosis of maternal infection, it is only reliable evidence of fetal infection if positive, and should be repeated later in gestation if negative.
Each year, thousands of children are born with or develop permanent disabilities such as hearing loss, vision loss, motor and cognitive deficits from congenital CMV infection (cCMV). However, awareness of cCMV and its associated sequelae is very low in pregnant women and healthcare providers. Both targeted and universal approaches to screen newborns for CMV infection are now achievable due to recent scientific advances including the development of a rapid, high-throughput method for detecting CMV in saliva, the efficacy of antiviral treatment in symptomatic infants, and the demonstration of cost effectiveness of CMV screening. Future studies are needed to address gaps in our understanding on the role of non-primary maternal CMV infections, the evaluation of antiviral treatment in asymptomatic infants, and the implementation of prevention strategies for cCMV.

View all citing articles on Scopus

^☆: Supported in part by grants from the Ministry of Public Health (Instituto Superiore di Sonite, AIDS Project), the Ministry of Education, Scientific and Technological Research, and the University of Bologna.

^☆☆: Reprint requests: Brunella Guerra, MD, PhD, Clinica Ostetrica e Ginecologica II, Policlinico S. Orsola, Via Massarenti 13, 40138 Bologna, Italy.

View full text

Fetus-Placenta-NewbornPrenatal diagnosis of symptomatic congenital cytomegalovirus infection☆,☆☆

Abstract

Section snippets

Study population

Results

Comment

Acknowledgements

Cytomegalovirus infection: congenital and neonatal disease

Scand J Infect Suppl

Symptomatic congenital cytomegalovirus infection: neonatal and mortality

Pediatr Infect Dis J

The outcome of congenital cytomegalovirus in relation to maternal antibody status

N Engl J Med

The megalovirus [editorial]

Ultrasound Obstet Gynecol

Congenital cytomegalovirus disease: a NOW problem

J Infect Dis

Cytomegalovirus infection in the pregnant mother, fetus, and newborn infant

Clin Perinatol

Prenatal diagnosis of fetal primary cytomegalovirus infection

Obstet Gynecol

Improved prenatal diagnosis of congenital human cytomegalovirus infection by a modified nested polymerase chain reaction

J Med Virol

Prenatal diagnosis of congenital cytomegalovirus infection

J Clin Microbiol

Anticytomegalovirus (anti-CMV) immunoglobulin G avidity in identification of pregnant women at risk of transmitting congenital CMV infection

Clin Diagn Lab Immunol

Avidity of immunoglobulin G directed against human cytomegalovirus during primary and secondary infections in immunocompetent and immunocompromised subjects

Clin Diagn Lab Immunol

Value of cytomegalovirus (CMV) IgG avidity index for the diagnosis of primary CMV infection in pregnant women

J Infect Dis

Fetus-Placenta-Newborn
Prenatal diagnosis of symptomatic congenital cytomegalovirus infection☆,☆☆