In this case description, we present a rare manifestation of cCMV, characterized by cerebral hemorrhage and cardiomyopathy.

As the neonate presented with perinatal asphyxia, thrombocytopenia was initially attributed to asphyxia and therapeutic hypothermia (TH). The possibility of a CMV viral sepsis as the underlying cause of asphyxia and thrombocytopenia was not initially suspected in our patient, because of the previous maternal CMV immunization. In fact, the brain MRI findings in our patient did not suggest perinatal asphyxia. Severe HIE in term infants affects primarily gray matter, especially the basal ganglia and thalamus [13]. Instead, there was an involvement of the periventricular areas; the biventricular and frontal intraparenchymatous hemorrhages on MRI were not specific to cCMV but were rather due to thrombocytopenia and coagulopathy.

Only three other case reports were published in the last 10 years [14,15,16] about neonates with severe cCMV born by previously immune women. We compared them to our case (Table 2).

Our case highlights the potential severity of cCMV infection even in previously immune mothers: the severe thrombocytopenia was responsible for a severe intraventricular hemorrhage and provoked a cardiomyopathy. Thrombocytopenia is a consistent finding in all the case reports and is well-known to be associated with cCMV infection. In the case report from Stoykova et al. [14], the newborn presented with a massive intraventricular hemorrhage shown by MRI, like in our case. Both cases that experienced cerebral hemorrhage also presented with seizures.

cCMV infection can mimic bacterial sepsis. In 3 out of 4 reported cases, including our own, treatment with broad-spectrum antibiotics was initiated [14, 16]. In the case described by Stoykova et al. [14], the patient was born at 30 weeks of gestational age with extremely severe general conditions and presented with an Apgar of 1/1/3 at 1, 5 and, 10 min, respectively. He had pale skin, petechial rash and generalized edema. Artificial ventilation was needed, and cardiac ultrasound showed evidence of cardiomegaly and left ventricular hypertrophy. In the case described by Arnout et al. [16] the patient was born at term. Apgar scores were 6,6 and 7, respectively. Physical examination showed mild respiratory distress, hepatosplenomegaly, petechiae, facial dysmorphic features and axial hypotonia. Non-invasive ventilation was needed, and empirical antibiotic therapy was started for suspected sepsis. In our case, the patient was born at term. Apgar scores were at 1/4/9. He fulfilled the criteria for TH and later developed seizures. All 3 cases could have been explained by bacterial sepsis. Because of the mothers’ CMV immune status, there was a delay in diagnosis in all 3 cases.

Cardiomyopathy and cardiac dysfunction due to CMV has often been described in adults and older children. There are very few cases described in the literature related to congenital infections.

Stoykova et al. [14], described a patient who presented cardiomegaly and left ventricular hypertrophy. Our patient had severe cardiac failure with an ejection fraction of 33% and signs suggestive of cardiomyopathy. It was only after discovering the cardiac involvement that we thought of performing a viral screening in our patient, which led to the late diagnosis of cCMV. CMV infection can lead to cardiomyopathy through several mechanisms. The virus may directly infect cardiac cells, causing inflammation and damage to the heart muscle. Additionally, CMV-induced immune responses can trigger an inflammatory cascade, contributing to the development of cardiomyopathy by disrupting the normal functioning of the heart tissue [17, 18].

Mothers that are immune to CMV before pregnancy are currently not screened for CMV reactivation, because of the low probability of maternal fetal transmission, ranging from 0.5 to 1.5% [5]. Nevertheless, in the unlikely case of transmission, the severity of congenital CMV remains high.

The possibility of cCMV infection as the underlying cause of thrombocytopenia, cerebral hemorrhage and septic status was not initially suspected in our patient. Incorporating universal neonatal screening for cCMV as a standard protocol could have expedited the diagnosis, potentially preventing the cerebral hemorrhage.

There is ongoing debate regarding universal CMV testing of all newborns at birth. Our case report highlights the importance of an early diagnosis of cCMV infection. In fact, the early diagnosis of cCMV can lead to the early initiation of antiviral therapies and reduce neurological impairments and sequelae.

According to the European Expert Consensus, newborns with a maternal history of CMV infection during pregnancy, those who are symptomatic, and infants with sensorineural hearing loss should be screened for CMV infection [12]. Studies have shown that approximately half of cCMV infections were due to maternal non-primary infection during pregnancy [4].

The diagnosis of cCMV infection requires the presence of viral nucleic acid or a replicating virus within the first three weeks of life. After this period, it can be difficult to assess whether the infection is postnatally acquired [6]. The dried blood spot (Guthrie card) is a reliable method for confirming cCMV infection retrospectively [8], but its low sensitivity limits its value as a screening test [19]. In our case, the patient’s mother’s CMV serologies were not repeated during pregnancy, but the presence of CMV DNA on the Guthrie card performed at birth, confirmed cCMV infection.

In conclusion, this case report highlights the insidious presentations of cCMV infection. Cerebral hemorrhage and cardiac damage are rarely described in the literature, but cCMV infection must be included in their differential diagnosis. This case also serves as a reminder that, although rare, congenital CMV infection in a newborn from an immunized mother can be extremely severe.

In our view, it is essential to reconsider the discussion surrounding the universal screening of newborns and the ongoing screening of immunized mothers.