Congenital Cytomegalovirus Infection in the Absence of Maternal Cytomegalovirus-IgM Antibodies.

BACKGROUND: Congenital cytomegalovirus (cCMV) infections are the most prevalent intrauterine infections worldwide and are the result of maternal primary or non-primary infections. Early maternal primary infections are thought to carry the highest risk of fetal developmental abnormalities as seen by ultrasound; however, non-primary infections may prove equally detrimental. METHODS/RESULTS: This case series presents 5 cases with fetal abnormalities detected in the second and third trimester, in which cCMV infection was ruled out due to negative maternal CMV-IgM. DISCUSSION: This series highlights the possible pitfalls in serology interpretation and fetal diagnosis necessary for appropriate parental counseling. Once fetal abnormalities have been confirmed and cCMV is suspected, maternal CMV serostatus and fetal infection should be determined. Maternal CMV serology may be ambiguous; therefore, caution should be exercised when interpreting the results.

Outcome of Preterm Infants With Postnatal Cytomegalovirus Infection.

OBJECTIVES: To assess whether preterm infants with postnatal cytomegalovirus infection develop neurologic sequelae in early childhood. METHODS: Infants <32 weeks' gestation were prospectively screened for cytomegalovirus (CMV) at term-equivalent age. Neurodevelopment was compared between CMV-positive and CMV-negative infants by using the Griffiths Mental Development Scales (GMDS) at 16 months' corrected age (CA); the Bayley Scales of Infant and Toddler Development, Third Edition or the GMDS at 24 to 30 months' CA; and the Wechsler Preschool and Primary Scale of Intelligence, Third Edition and Movement Assessment Battery for Children, Second Edition at 6 years of age. At 6 years old, hearing was assessed in CMV-positive children. RESULTS: Neurodevelopment was assessed in 356 infants at 16 months' CA, of whom 49 (14%) were infected and 307 (86%) were noninfected. Infected infants performed significantly better on the GMDS locomotor scale. There were no differences at 24 to 30 months' CA on the Bayley Scales of Infant and Toddler Development, Third Edition or GMDS. At 6 years of age, infected children scored lower on the Wechsler Preschool and Primary Scale of Intelligence, Third Edition, but mean scores were within normal range, reaching significance only in verbal IQ (96 [SD 17] vs 103 [SD 15] points; P = .046). Multiple regression indicated no impact of CMV status but significant influence of maternal education and ethnicity on verbal IQ. No significant differences in motor development were found and none of the infected children developed sensorineural hearing loss. CONCLUSIONS: In this cohort study, postnatal cytomegalovirus infection in preterm children did not have an adverse effect on neurodevelopment within the first 6 years of life.

Neuro-imaging findings in infants with congenital cytomegalovirus infection: relation to trimester of infection.

BACKGROUND: Congenital cytomegalovirus (cCMV) infection early in pregnancy may result in major disabilities. Cerebral abnormalities detected using cranial ultrasound (cUS) and magnetic resonance imaging (MRI) have been related to neurological sequelae. OBJECTIVE: To evaluate the additional value of MRI and assess the relationship between time of infection during pregnancy and outcome in infants with cCMV infection. METHODS AND STUDY DESIGN: Demographic and clinical data were collected in infants with cCMV infection (1992-2013). Trimester of infection, neuro-imaging results and outcome were reviewed. Cerebral abnormalities were categorized into none, mild (lenticulostriate vasculopathy, germinolytic cysts, high signal intensity on T2-weighted images) and severe (migrational disorder, ventriculomegaly, cerebellar hypoplasia). Results were statistically analysed. RESULTS: Thirty-six infants were eligible for analysis. cUS was performed in all and cranial MRI in 20 infants. Migrational disorders were only diagnosed using MRI (p < 0.01). In 17 infants trimester of infection was ascertained. Seven out of 10 infants infected during the first trimester had severe abnormalities on cUS (5 confirmed on MRI) and adverse sequelae; 3 had no/mild abnormalities on cUS/MRI and normal outcome. Two out of 3 infants infected during the second trimester with no/mild abnormalities on cUS/MRI had normal outcome; 1 with mild cUS and MRI abnormalities developed sensorineural hearing loss. Four infants infected during the third trimester with no/mild abnormalities on cUS/MRI had normal outcome. CONCLUSION: Infants with a first trimester cCMV infection are most at risk of severe cerebral abnormalities and neurological sequelae. MRI, and not cUS, enables an early diagnosis of migrational disorders, which can improve prediction of outcome.

Predictors of severity for postnatal cytomegalovirus infection in preterm infants and implications for treatment.

Postnatal cytomegalovirus (CMV) infection is common in neonates and is mostly acquired through infected breast milk from seropositive mothers. In this review, risk factors of postnatal CMV transmission and predictors of severity, preventive measures and treatment of symptomatic postnatal CMV infection in preterm infants are discussed. Several viral, transmission route and host factors have been associated with a higher risk of postnatal CMV transmission from mother to child. Severity predictors of symptomatic postnatal CMV infection may include extreme prematurity (gestational age <26 weeks), timing of postnatal infection as well as comorbidities. Further research in postnatally infected preterm infants at risk for severe symptoms is essential with respect to preventive measures involving the infected breast milk and antiviral treatment.

Reduced occipital fractional anisotropy on cerebral diffusion tensor imaging in preterm infants with postnatally acquired cytomegalovirus infection.

BACKGROUND: Detection of white matter (WM) abnormalities on MRI is important regarding the neurodevelopmental outcome in preterm infants. The long-term neurodevelopmental outcome of preterm infants with postnatal cytomegalovirus (CMV) infection has not been studied extensively. OBJECTIVES: We aimed to assess WM microstructure in preterm infants with postnatal CMV infection using diffusion tensor imaging. METHODS: Infants <32 weeks' gestational age (GA) admitted to our hospital between 2007 and 2010, who had cerebral diffusion tensor imaging at term-equivalent age (40 weeks' GA) were included. CMV PCR in urine collected at term-equivalent age was performed to diagnose postnatal CMV infection. Congenital infection was excluded. In the frontal, parietal and occipital WM mean diffusivity, fractional anisotropy (FA), radial and axial diffusivity were calculated. Neurodevelopmental outcome was assessed at 16 months' corrected age using Griffiths' Mental Developmental Scales. RESULTS: Twenty-one postnatally infected and 61 noninfected infants were eligible. Both groups were comparable regarding GA, birth weight and age at MRI. There was a significant difference in median FA of the occipital WM between infected and noninfected infants (0.13 [IQR 0.11-0.16] versus 0.16 [IQR 0.14-0.18], p = 0.002). There were no differences in short-term neurodevelopmental outcome between infected and noninfected infants. CONCLUSIONS: A significantly reduced FA suggests microstructural changes in the occipital WM of postnatally infected infants. These microstructural changes do not appear to result in impaired neurodevelopmental outcome at 16 months' corrected age.