Assessment of prenatal imaging, fetal blood parameters, and new pharmacological interventions, in congenital cytomegalovirus infection

Abstract

[eng] Cytomegalovirus (CMV) remains a major cause of congenital infection and disease during pregnancy with around 0.2-2% newborns being infected at birth. Congenital infection with Human CMV (cHCMV) is the first cause of non-genetic sensorineural hearing loss (SNHL), and an important cause of neurological impairments, vision loss and neurodevelopmental delay.2–4 The prevalence of cCMV varies according to the population, with an estimated 40 to 100% of individuals being infected.3 The seroprevalence tends to be higher in lower socio-economic groups, racial and ethnic minority populations, and women of higher parity and advanced maternal age CMV infection is acquired through close contact with saliva and urine mostly from young children and through sexual intercourse. After CMV primary infection, the virus can be continuously or intermittently excreted for months or years.6 Fetal infection may occur after primary as well as after non-primary maternal infection (reactivation or reinfection by a different strain). As a result of the high seroprevalence, there is a continuously high reservoir of CMV in the population. Non-immune pregnant women with young children in daycare are at higher risk of infection due to high rates of horizontal transmission through saliva among young children. Since clinical symptoms are usually absent, the only reliable way to estimate the prevalence of infection in a population is through laboratory testing. CMV can be transmitted from mother to the fetus anytime during gestation (in-utero, intrapartum, or during breast-feeding) but is most likely to cause serious permanent damage to the fetus when the mother develops infection during the first trimester of pregnancy.4,7 Intrauterine transmission is thought to be the result of trans-placental crossing of the virus, which then replicates in multiple embryonic or fetal tissues.8 After primary infection the risk of vertical transmission is around 32%9–12, being much lower (£3.5%) after non-primary infection. According to Chatzakis et al. the pooled rates of vertical HCMV transmission with maternal primary infection (MPI) are 5.5%, 21%, 37%, 40% and 66% in the preconception period and periconception periods, and the first, second and third trimester, respectively. The rate of fetal insult after MPI was higher in the preconception period and first trimester of pregnancy with 29% and 19%, respectively; whereas in the second and third trimester the pooled rate of fetal insult was not greater than 1%. In MPI with transmission to the fetus during the first trimester of pregnancy12, the percentage of congenitally infected

symptomatic children with permanent sequelae is estimated to be 28%, whereas the percentage of children without symptoms at birth who later develop hearing loss is estimated to be 13.5%. Both, the diagnosis of primary infection early in pregnancy and the presence of compatible fetal signs on ultrasound (US) allow the diagnosis of CMV infection in the fetus. Viral DNA detection by polymerase chain reaction (PCR) in the amniotic fluid has been recognized as the reference method for the diagnosis of fetal infection. To achieve an accurate diagnosis the procedure must be performed after 17 weeks of pregnancy and at least 8 weeks after maternal infection.16,17 The sensitivity of PCR in amniotic fluid has been reported to be between 90 to 95% with a 5 to 10% false negative rate explained by late trans-placental passage of the virus. The morbidity of the cCMV in infancy, including hearing loss and neurodevelopmental delay, has been associated with abnormal prenatal US and magnetic resonance imaging (MRI) findings. However, direct extrapolation of the neonatal syndrome to the fetus is difficult.

[spa] Antecedente: El citomegalovirus humano (HCMV) es una de las principales causas de infección congénita en todo el mundo. La infección congénita por citomegalovirus (CMV) es una causa importante de pérdida auditiva neurosensorial, retraso en el desarrollo neurológico, epilepsia y pérdida de visión. Hipótesis principal: la precisión diagnóstica/pronóstica prenatal para predecir qué embarazos resultarán en un feto/recién nacido sintomático en la infección congénita por CMV puede mejorar mediante una combinación de pruebas biológicas en sangre fetal, marcadores ecográficos y/o por resonancia magnética (RM). Objetivos: Evaluar el valor pronóstico de los hallazgos por ecografía y/o por RM fetal junto con el análisis de parámetros en sangre fetal en una serie de fetos con o sin infección comprobadas por CMV. Evaluar los efectos de la terapia antiviral materna con valaciclovir (VCV) tanto para disminuir la transmisión vertical del virus (prevención primaria) como la carga viral en el recién nacido y la evolución de las lesiones ecográficas prenatales. Metodología: estudio ambispectivo donde incluimos fetos con infección por CMV confirmada en muestra de líquido amniótico y fetos sin infección CMV. La severidad de la infección/afectación fetal se determinó de acuerdo a los hallazgos, en estudio de imagen, ya sea por ultrasonido obstétrico detallado y/o por RM, del sistema nervioso central (SNC). Los fetos fueron categorizados como afectación leve o severa.