Long-term Outcomes after Postnatal Cytomegalovirus Infection in Low Birthweight Preterm Infants

Abstract

Background: Cytomegalovirus (CMV) is the most common viral infection seen in newborns. Although postnatally acquired CMV (pCMV) infection rarely results in serious manifestations in term infants, preterm infants can develop severe clinical illness. However, the long-term implications of pCMV infection of preterm infants are unknown. Few robust studies on longterm outcomes of pCMV infection have been performed, and those reported often present conflicting results. Our objective was to assess the long-term outcomes for low birthweight (LBW) preterm infants after pCMV infection. Methods: A systematic review of English and non-English articles using MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, CINAHL, and Web of Science was conducted. Search strategies included a mix of keywords and database-specific subject headings for CMV and LBW infants. Editorials, comments, reviews and animal-only studies were excluded. Case reports, observational, experimental and randomized controlled trials that examined pCMV in preterm or VLBW infants and longterm (>1 month) impact of pCMV were included. Results: pCMV infection in preterm infants is associated with increased risk for pulmonary and neurologic complications and increases length of stay. There is less evidence to suggest that pCMV is associated with necrotizing enterocolitis, ophthalmologic, audiologic and anthropomorphic complications in preterm infants. Conclusions: Preterm infants with pCMV, especially those with symptomatic infection, may have long-term pulmonary and neurodevelopmental morbidity compared with their pCMV negative counterparts. Our results highlight the importance of pCMV detection and prevention in preterm infants in the neonatal intensive care unit. Large prospective studies are needed to fully define outcomes and determine if treatment improves outcomes.

Postnatal Cytomegalovirus Infection: Is it Important? A 10-Year Retrospective Case-control Study of Characteristics and Outcomes in Very Preterm and Very Low Birth Weight Infants

“…13 There are conflicting data regarding LOV and LOS in the literature, however collective evidence from a recent systematic review indicates that pCMV infection may be associated with increased LOV and LOS, particularly in symptomatic infants. 39 These are important findings as increased LOV confers an increased risk for nosocomial and secondary bacterial infections 41 and BPD. 40 Increase in LOS is associated with increased costs to the healthcare system 42 which are already substantial in this preterm population.…”

“…We did not identify a significant difference in the incidence of SNHL, in concordance with the literature. 39 One pCMV-positive infant had a mild bilateral SNHL; however, this infant’s congenital 7q22 chromosomal deletion is also associated with hearing loss. 48…”

“…A recent systematic review synthesizing the collective data suggests that pCMV-positive infants, especially symptomatic infants, are at increased risk for worsening respiratory status and BPD. 39 This association of CMV and respiratory compromise may be due to direct CMV-mediated cytopathic damage to the lung parenchyma, indirect damage through an invoked inflammatory response, 11,13 and increased LOV due to CMV-SLS. 40 PCMV-positive infants in our study had significantly increased LOV and LOS compared to controls, independent of confounders, with periods of ventilation twice as long and hospital admissions 30 days longer than controls.…”

Clinical, Virologic and Immunologic Correlates of Breast Milk Acquired Cytomegalovirus (CMV) Infections in Very Low Birth Weight (VLBW) Infants in a Newborn Intensive Care Unit (NICU) Setting

“…We also observed an increased need for O 2 therapy both at 36 weeks of corrected GA ( p < 0.05) and at the time of home discharge ( p < 0.01). Previous reports have noted an association between post-natal breast-milk-acquired CMV and lung disease, including BPD [ 6 , 7 , 27 , 28 , 29 ]. The role of perinatal breast-milk-acquired CMV in the pathogenesis of long-term disabilities, including SNHL, remains incompletely defined.…”

“…Extensive evidence documents the short-term morbidities that can be associated with such infections [ 2 , 3 , 18 , 19 , 37 ]. Although the information is incomplete, there is increasing evidence that such infections in VLBW increase the risk of long-term chronic lung disease, and possibility SNHL, as well as other neurodevelopmental disabilities [ 5 , 6 , 7 , 29 ]. Considerations for mitigating risk have been the subject of a recent review [ 2 ], and have included freezing or pasteurization of milk; maternal serological screening to identify CMV-seropositive women at risk for reactivation of CMV during lactations; actual testing of breast milk itself before feeding, using rapid, point-of-care testing platforms; or the addition of antiviral factor, including an antibody, to inactivate a virus without destroying the salutary components of breast milk (which occurs with pasteurization and, to a lesser but important extent, freezing).…”