FV 695. Does Early Postnatal hCMV Infection Have Long-Term Consequences on Brain Structure of Former Preterm Born Children?

Background: Congenital infection with human cytomegalovirus (hCMV) is the most common nongenetic cause of severe innate mental disability, while a postnatal infection with hCMV in a full-term born infant does not have long-term sequelae. In preterm born infants, however, long-term consequences of an early postnatal infection with hCMV are still controversial. In previous neuropsychological and functional MR studies, we could already show additional long-term effects of such an infection.

Aims: Analyzing long-term influences of early postnatal hCMV infection on brain structure in former preterm born children.

Research question: Does early postnatal hCMV infection have long-term consequences on brain structure of former preterm born children?

Methods: Data of 37 preterm born participants (PT), ≤32 weeks of gestation, and/or ≤1,500 g gestational weight were analyzed. All were initially hCMV negative. Throughout early postnatal hospitalization, 14 contracted hCMV via breast milk (PT_hCMV+), while 23 did not (PT_hCMV−). Additionally, 38 healthy, full-term born participants were included (FT).

At 13.6 years median age (SEM: 0.3), T1-weighted 3D datasets (TR/TE = 1,300/9.92 milliseconds, resolution 1 × 1 × 1 mm³) were acquired using a 1.5-T Avanto MR-scanner (Siemens, Erlangen). Data were preprocessed in CAT12, a toolbox in SPM12, running on Matlab (R2014b). Data were processed using self-generated pediatric reference data. Local gray matter volume was analyzed using voxel-based morphometry (VBM), while cortical thickness was analyzed using surface-based morphometry. Analyses were corrected for gender and age as well as (in volume-based analyses) for global volume differences via global scaling. We corrected for multiple comparisons via threshold-free cluster enhancement and familywise error rate (FWE, p < 0.05). Global volumes were analyzed using a Mann–Whitney’s U test (p < 0.05, Bonferroni corrected).

Results: PT showed a significant decrease in global gray matter volume compared with FT. Few additional local gray matter volume differences were found in VBM analyses. Surface-based analyses showed few clusters of increased cortical thickness in PT versus FT.

When comparing global gray matter volume of PT_hMCV− and PT _hCMV+ versus FT, only PT_hCMV− showed significantly decreased volumes. Comparing PT_hCMV− versus PT_hCMV+, PT_hCMV+ had a tendency toward increased global gray matter volume, which, however, did not reach significance. Analyses of local gray matter volume showed no significant differences. However, PT_hCMV+ showed substantial and widespread increases in cortical thickness when compared with PT_hCMV−.

Conclusion: In agreement with previous studies, our former preterm born participants showed decreased global and local gray matter volumes. Counter-intuitive increase of global gray matter volume in hCMV-infected former preterm born children could be explained by widespread increases of cortical thickness. This effect may reflect impaired cortical maturation due to impaired cortical proliferation and/or organization. Especially considering effects of intrauterine hCMV infection on cortical organization, this explanation seems plausible.

To conclude, our results demonstrate that an early postnatal hCMV infection has long-term consequences on brain structure of former preterm born children. Initially, counter-intuitive results could only be explained by the combination of several analytical approaches. Therefore, efforts to avoid early-postnatal hCMV infection in preterm born infants should continue to be implemented.

 

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No conflict of interest has been declared by the author(s).