Long‐term neurobiological consequences of early postnatal hCMV‐infection in former preterms

Abstract

Early postnatal infection with human cytomegalovirus (hCMV) may contribute to an adverse cognitive outcome in early preterm-born children (PT). We here set out to explore whether long-term neurobiological consequences of such an infection are detectable using fMRI in children and adolescents who were born very preterm and who either did (PThCMV+ ) or did not (PT(hCMV-)) suffer from an early postnatal hCMV-infection, when compared with typically developing healthy control (HC) subjects. Overall, data from 71 children and adolescents could be included, 34 PT (of which 15 were PT(hCMV+) and 19 were PT(hCMV-)) and 37 HC. Using a recently established "dual use" fMRI task, we investigated language and visuospatial functions. There were significant activation differences in the left hippocampus (PT > HC and PT(hCMV+) > HC), and in the right anterior cingulate cortex (PT(hCMV-) > PT(hCMV+)) when performing the language task. Surprisingly, only a small region in the occipital cortex showed a significant activation difference (HC > PT(HCMV-)) when performing the visuospatial task. Targeted analyses revealed differences in gray matter volume, but not density, in several brain regions. Our results suggest that long-term neurobiological consequences of an early postnatal hCMV infection are detectable even in older children and adolescents formerly born very preterm, compatible with a higher effort when performing a cognitive task. This suggests that measures to prevent such an infection are warranted. Furthermore, an interrelation of brain structure and function was detected that may constitute a severe confound when using fMRI to compare structurally differing groups.

Postnatal Human Cytomegalovirus Infection in Preterm Infants Has Long-Term Neuropsychological Sequelae

“…This infection entails primary adverse events, such as inflammation, and less specific secondary infectious sequelae, such as hypotension, bradycardia, or apnea. Although overt lesions were equally rare in the 2 preterm groups (both 21%), more sophisticated MRI analyses of our samples indicate that the performance differences might be explained by subtle neural alterations (eg, regional differences in functional activation 15 or disturbances within the neural networks 31 ). Combined with our behavioral data, these findings indicate that the CMV infection may make a difference for the preterm infant's early postnatal brain development.…”

“…The entire sample participated in observational studies on neonatal transmission rates, 14,15 and follow-up results of parts of our sample have been previously published, with respect to neurodevelopmental outcome between 2 and 4 years, 10 between 4 and 8 years, 13 and between 6 and 8 years. 14 The current study sample includes children between 11 and 17 years ( Table I) who underwent neuropsychological, neurologic, and magnetic resonance imaging (MRI) examinations.…”

“…Typically, developing children in group TERM between 11 and 17 years were recruited in the summer of 2010 by local press and public announcements. Exclusion criteria for all participants were psychiatric disorders, hearing deficits, and general MRI contraindications (because MRI data were required as part of this project, the results of which are reported elsewhere 15 ). For the group TERM, no objective neonatal data was available, nor were they formally screened for CMV infection in the neonatal period.…”

“…Maternal education level was assessed in years of formal education (#9: "lower"; 10-11: "middle"; 12-13: "upper"; >13: "higher" education. 15 ). In the course of the current 19 Neonatal characteristics (bronchopulmonary dysplasia, retinopathy of prematurity, intracerebral hemorrhage, birth weight percentile) were drawn from clinical charts.…”

Symptomatic Postnatal Cytomegalovirus Testing among Very Low-Birth-Weight Infants: Indications and Outcomes

“…[2][3][4] The majority of prospective and casecontrol studies of postnatal CMV infection among VLBW infants have reported no difference in clinical outcomes, 5-9 although recent studies have found negative impacts on long-term neurodevelopmental outcomes. [10][11][12] Prior studies have included few symptomatic CMV-positive infants, and many asymptomatic, infected infants identified only by prospective screening. 7,9,13 These studies could reassure neonatal clinicians that most instances of postnatal CMV have little impact on VLBW infants.…”