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

## TL;DR

Early postnatal human Cytomegalovirus infection in preterm infants may have lasting effects on brain structure beyond those caused by prematurity alone.

## Contribution

This study reveals distinct long-term cerebral consequences of early postnatal hCMV infection in preterm-born children.

## Key findings

- Preterm-born children showed lower global gray matter volumes compared to full-term children.
- Early postnatal hCMV infection was associated with higher cortical thickness in frontal brain regions in preterm-born children.
- The effects of hCMV infection on brain structure were distinct from those caused by prematurity alone.

## Abstract

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.

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+.

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.

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.

Cortical surface analyses of former preterm‐born children with (PT hCMV+) and without (PT hCMV−) early postnatal human Cytomegalovirus (hCMV) infection at ∼13 years of age. Note the strong effect of prematurity when compared to full‐term‐born children (FT, top), but the independent and even more widespread effect of HCMV infection (bottom).