Blood genome expression profiles in infants with congenital cytomegalovirus infection.

Congenital CMV infection (cCMVi) affects 0.5-1% of all live births worldwide, making it the leading cause of sensorineural hearing loss (SNHL) in childhood. The majority of infants with cCMVi have normal hearing at birth, but are at risk of developing late-onset SNHL. Currently, we lack reliable biomarkers to predict the development of SNHL in these infants. Here, we evaluate blood transcriptional profiles in 80 infants with cCMVi (49 symptomatic, 31 asymptomatic), enrolled in the first 3 weeks of life, and followed for 3 years to assess emergence of late-onset SNHL. The biosignatures of symptomatic and asymptomatic cCMVi are indistinguishable, suggesting that immune responses of infants with asymptomatic and symptomatic cCMVi are not different. Random forest analyses of initial samples in infants with cCMVi, irrespective of their clinical classification, identify a 16-gene classifier signature associated with the development of SNHL with 92% accuracy, suggesting its potential value as a biomarker.

Evaluation of clinically asymptomatic high risk infants with congenital cytomegalovirus infection.

OBJECTIVE: To determine the frequency of abnormal findings on evaluation of neonates with congenital CMV infection who have a normal physical examination STUDY DESIGN: Retrospective, 2-center study (1996-2017) that reviewed results of complete blood cell count and platelets, serum alanine aminotransferase (ALT) and bilirubin concentrations, eye examination, cranial ultrasonography or other neuroimaging, and brainstem evoked responses performed on neonates with congenital CMV infection and a normal physical examination RESULTS: Of 34 infants with congenital CMV infection and a normal physical examination, 56% (19/34) had ≥1 abnormality: 39%, elevated ALT concentration; 45%, abnormal neuroimaging (five, lenticulostriate vasculopathy; six, intraventricular hemorrhage; four, calcifications); 12%, anemia; 16%, thrombocytopenia; and 3%, chorioretinitis. Seven (21%) infants had sensorineural hearing loss, and 18 infants received antiviral therapy. CONCLUSION: Some infants with congenital CMV infection and a normal physical examination had abnormalities on laboratory or neuroimaging evaluation, which in some cases prompted antiviral treatment.

Age-specific gray and white matter DTI atlas for human brain at 33, 36 and 39 postmenstrual weeks.

During the 3rd trimester, dramatic structural changes take place in the human brain, underlying the neural circuit formation. The survival rate of premature infants has increased significantly in recent years. The large morphological differences of the preterm brain at 33 or 36 postmenstrual weeks (PMW) from the brain at 40PMW (full term) make it necessary to establish age-specific atlases for preterm brains. In this study, with high quality (1.5 × 1.5 × 1.6 mm3 imaging resolution) diffusion tensor imaging (DTI) data obtained from 84 healthy preterm and term-born neonates, we established age-specific preterm and term-born brain templates and atlases at 33, 36 and 39PMW. Age-specific DTI templates include a single-subject template, a population-averaged template with linear transformation and a population-averaged template with nonlinear transformation. Each of the age-specific DTI atlases includes comprehensive labeling of 126 major gray matter (GM) and white matter (WM) structures, specifically 52 cerebral cortical structures, 40 cerebral WM structures, 22 brainstem and cerebellar structures and 12 subcortical GM structures. From 33 to 39 PMW, dramatic morphological changes of delineated individual neural structures such as ganglionic eminence and uncinate fasciculus were revealed. The evaluation based on measurements of Dice ratio and L1 error suggested reliable and reproducible automated labels from the age-matched atlases compared to labels from manual delineation. Applying these atlases to automatically and effectively delineate microstructural changes of major WM tracts during the 3rd trimester was demonstrated. The established age-specific DTI templates and atlases of 33, 36 and 39 PMW brains may be used for not only understanding normal functional and structural maturational processes but also detecting biomarkers of neural disorders in the preterm brains.