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Four cases of serious congenital cytomegalovirus (CMV) infections are described in this report. All cases were diagnosed postnatally using cerebrospinal fluid (3/4) or blood PCR (1/4) and histochemical study of the placenta (4/4). All infants were born prematurely. Maternal factors identified as significant were younger age at pregnancy and those from low-income social strata. The major clinical findings among patients with congenital CMV infection were hydrocephalus and persistent thrombocytopenia. The children's clinical condition did not improve over the course of the disease, leading to complications associated with extreme prematurity. Two of the children died, one of whom had severe brain malformations and showed neurological compromise at follow-up, seizures, motor impairment, and severe cognitive delay. It is essential to perform antenatal screening for possible CMV infection among pregnant women, even in countries with high population seropositivity, such as Mexico, to establish prenatal interventions to reduce the risk of fetal damage., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Saúl Flores-Medina et al.)