Early Postnatal Infection With Human Cytomegalovirus Has Long-Term Consequences on Brain Structure of Former Preterm Born Children

Abstract

Purpose: Congenital infection with human Cytomegalovirus (hCMV) is a common cause of severe neurodevelopmental disability, while postnatal infection of a term-born infant will usually not lead to an adverse neurodevelopmental outcome. In preterm-born infants, long-term consequences of an early postnatal hCMV infection (usually via breast milk) are still controversial. This is highly relevant as preventative measures exist.

Methods: Data of 37 preterm-born children (PT; ≤ 32 weeks of gestation and/or weighing ≤ 1500 g) was included. Of these, 14 acquired an early postnatal infection with hCMV (PT _hCMV+), while 23 did not (PT _hCMV-). Further, 38 healthy term-born participants (FT) were included. Overall median age was 13.6 years (range 7.9-17.8 years). Global and local tissue volumes and brain surface parameters were analyzed. Consequences of prematurity were detected by comparing FT and PT, and sequelae of hCMV infection by comparing PT _hCMV- and PT _hCMV+.

Findings: Compared to FT, PT showed lower global gray matter (GM); interestingly, PT _hCMV+ showed a trend toward higher global GM than PT _hCMV-. Several clusters of local GM differed in volume between PT and FT, but none as a function of hCMV infection. Surface analyses between PT and FT identified predominantly right-hemispheric regions of lower cortical thickness in PT. Unexpectedly, widespread clusters of higher cortical thickness were found bilaterally in predominantly frontal brain regions in PT _hCMV+ compared to PT _hCMV-, demonstrating a lasting effect of hCMV infection.

Conclusion: We found lower global and local GM volumes due to of prematurity. Additionally, we demonstrate long-term effects of early postnatal hCMV infection on brain structure in PT, markedly different from those resulting from prematurity alone. This suggests distinct long-term cerebral consequences of early postnatal hCMV infection in former preterm-born children above and beyond those attributable to prematurity. Consequently, efforts to avoid HCMV infection in preterm-born infants should be implemented.

Keywords: MRI surface analyses; MRI volumetric analyses; postnatal human Cytomegalovirus infection; premature birth.