Postnatal Cytomegalovirus Infection in Preterm Infants ≤28 Weeks: Maternal IgG Effector Function, Risk Factors, Viral Kinetics in Relation to Symptom Onset, and Clinical Outcomes in a Prospective Multicenter Study

BACKGROUND: Postnatal cytomegalovirus (pCMV) infection is a major concern in extremely preterm infants. However, the clinical and maternal immunological factors involved in pCMV transmission and related manifestations remain unclear. METHODS: This multicenter prospective cohort study included infants born at ≤28 weeks of gestation. Urine samples were collected within 13 days of life to exclude congenital CMV infection. Serial urine, blood, and breast milk were tested biweekly for CMV load. Maternal serum and breast milk were analyzed for CMV-specific antibodies, IgG subclasses, neutralizing activity, and Fc-mediated effector functions, including antibody-dependent cellular phagocytosis (ADCP). Postnatal CMV infection risk factors and hematological, respiratory, and neurological outcomes were analyzed. RESULTS: Among 139 infants, 84 (60%) had seropositive mothers. pCMV occurred in 14 cases, including 13 (15%) from seropositive mothers and one with an unknown serostatus. Risk factors included short gestational age, premature rupture of membranes (PROM >24 h), repeated antenatal betamethasone administration, and high breast milk CMV load. Notably, 46% (6/13) infants with pCMV experienced prolonged PROM (> 1 week). Maternal ADCP activity was significantly reduced in the pCMV group, whereas neutralizing titers were not predictive. Neutropenia was the most frequent manifestation, and its onset coincided with viremia. Electroencephalographic abnormalities were more common in infants with pCMV. CONCLUSIONS: pCMV infection in extremely preterm infants is associated with specific maternal factors and impaired maternal Fcγ-mediated effector function. High pCMV incidence in infants of seropositive mothers with prolonged PROM suggests intrapartum transmission. These findings may help in implementing targeted prevention and guide evaluations of neurodevelopmental outcomes.