Early predictors of neurodevelopmental outcome in symptomatic congenital cytomegalovirus infection.

OBJECTIVE: To determine the ability of neonatal clinical, audiologic, and computed tomography (CT) findings to predict long-term neurodevelopmental outcome in children with symptomatic congenital cytomegalovirus (CMV) infection. METHODS: Longitudinal cohort study of children (n = 41) with symptomatic congenital CMV infection evaluated at birth and followed up with serial age-appropriate neurodevelopmental testing. The performance of birth characteristics as predictors of long-term outcome were determined, and clinical and CT scoring systems were developed and correlated with intellectual outcome. RESULTS: Microcephaly was the most specific predictor of mental retardation (100%; 95% CI 84.5-100) and major motor disability (92.3%; 95% CI 74.8-99). An abnormality detected by CT was the most sensitive predictor for mental retardation (100%; 95% CI 82.3-100) and motor disability (100%; 95% CI 78.2-100). A highly significant (P <.001) positive correlation was found between head size at birth and the intelligence/developmental quotient (IQ/DQ). Approximately 29% of children had an IQ/DQ >90. There was no association between sensorineural hearing loss at birth and cognitive outcome. However, children with sensorineural hearing loss on follow-up (congenital and late-onset) had a lower IQ/DQ (P =.006) than those with normal hearing. CONCLUSIONS: The presence of microcephaly at birth was the most specific predictor of poor cognitive outcome in children with symptomatic congenital CMV infection, whereas children with normal findings on head CT and head circumference proportional to weight exhibited a good cognitive outcome.

Hemophilia morbidity, cognitive functioning, and academic achievement.

Data from the Hemophilia Growth and Development Study (HGDS) were used to evaluate the association between hemophilia morbidity, measured by abnormalities in coordination and gait (CG), and intellectual ability and academic achievement. The CG abnormalities observed in the HGDS participants (n = 333) were primarily due to hemophilia-related morbidity. Although HGDS participants performed within the average range for age on measures of intellectual ability, there were meaningful differences between CG outcomes at baseline and throughout the 4 years of study. Participants without CG abnormalities consistently achieved higher scores than those with CG abnormalities on Reading, Spelling, and Arithmetic subtests of the Wide Range Achievement Test-Revised. Our findings suggest that lowered achievement is related to the functional severity of hemophilia.

Cytomegalovirus reinfection in young children.

OBJECTIVE: To determine the frequency of reinfection with new cytomegalovirus (CMV) strains in children in group child-care environments. METHODS: Ninety-two CMV strains isolated serially from children attending child care centers were analyzed. Strains were obtained from 1986 to 1994, from 37 children attending one of six centers in the area of Cedar Rapids and Iowa City, Iowa. The CMV isolates were analyzed by a polymerase chain reaction-based algorithm using primers for the a-sequence, glycoprotein B, and major immediate early (MIE) genes of human CMV. The a-sequence polymerase chain reaction products were compared on the basis of size, and products derived from glycoprotein B and MIE genes were compared according to restriction fragment length polymorphisms. RESULTS: Children were between 8 months and 5 years 7 months of age at the time of CMV isolation. The number of isolates ranged from 2 to 6 per child, and the intervals between the first and last CMV isolation ranged from 11 weeks to more than 3 years. At least 7 (19%) of the 37 children had evidence of infection with more than one CMV strain. In six of these children, reinfection with distinct strains was confirmed by analysis of the MIE gene products of sequential CMV strains. CONCLUSIONS: Children who attend child care centers, like adults who are immunosuppressed or have multiple sexual partners, are at risk of being reinfected with distinct CMV strains.

Mondini dysplasia and congenital cytomegalovirus infection.

We report a case of bilateral temporal bone anomalies in a child with symptomatic congenital cytomegalovirus infection and severe, bilateral sensorineural hearing loss identified at 3 months of age. High-resolution temporal bone computed tomography (HRCT) revealed bilateral findings of a short, malformed cochlea lacking an interscalar septum, a short and wide internal auditory canal, and an enlarged vestibular aqueduct, features diagnostic of bilateral Mondini dysplasia. To determine the importance of this observation, we completed HRCT in five additional children between 7 months and 9 years of age who had evidence of symptomatic congenital cytomegalovirus infection. One child with profound sensorineural hearing loss had severe bilateral temporal bone dysplasia with a small cochlea lacking an interscalar septum, an abnormal vestibule, and a large cochlear aqueduct. Of the remaining four children, hearing thresholds ranged from normal to profoundly decreased, but their HRCT scans were normal to visual inspection. When inner ear dimensions of these temporal bones were compared with norms established by Pappas and coworkers, however, seven of the eight ears had short cochleas and narrow lateral semicircular canals, and three ears had short or narrow vestibules. These results indicate that congenital cytomegalovirus infection may cause anomalies or growth disturbances of the temporal bone.

Cytomegalovirus transmission in a Midwest day care center: possible relationship to child care practices.

The epidemiology of cytomegalovirus (CMV) infection and transmission in a large Iowa day care center was studied. Over the 9 months of the study the overall CMV prevalence rates were 21% to 22%, with rates as high as 71% in toddlers. Titers of CMV in the urine or saliva of infected children were as high as 3 X 10(4) plaque-forming units of CMV per milliliter, similar to titers of CMV observed in some congenitally infected infants. Restriction enzyme analysis of CMV isolates from children in the center demonstrated two major clusters with similar patterns, one among 2- and 3-year-old children and another among infants. The clustering of similar CMV isolates among nonambulatory infants suggests that child care or hygienic practices may contribute to the spread of CMV infection in day care centers. Furthermore, the relatively high prevalence of CMV excretion in this center and the low seropositivity rates to CMV among adults in Iowa suggest that adults in the Midwest who have contact with children in day care centers may be at risk for primary CMV infection.