Antolin M. Llorente

Cytomegalovirus urinary excretion and long term outcome in children with congenital cytomegalovirus infection.

Background. Cytomegalovirus (CMV) is the most frequent cause of congenital infection, and both symptomatic and asymptomatic infants may have long term sequelae. Children with congenital CMV infection are chronically infected and excrete CMV in the urine for prolonged periods. However, the effect of prolonged viral replication on the long term outcome of these children is unknown. Objective. To determine whether duration of CMV excretion is associated with outcome at 6 years of life in symptomatic and asymptomatic congenitally infected children. Methods. Longitudinal cohort study. Children congenitally infected with CMV were identified at birth and followed prospectively in a study of long term effects of congenital CMV infection. The relationship between duration of CMV urinary excretion and growth, neurodevelopment and presence and progression of sensorineural hearing loss (SNHL) at 6 years of age was determined. Results. There was no significant difference in the duration of viral urinary excretion between children born with asymptomatic (median, 4.55 years) and symptomatic (median, 2.97 years) congenital CMV infection (P = 0.11). Furthermore there was no association between long term growth or cognitive outcome and duration of viral excretion. However, a significantly greater proportion of children who excreted CMV for <4 years had SNHL and progressive SNHL compared with children with CMV excretion >4 years (P = 0.019, P = 0.009, respectively). Conclusions. Children congenitally infected with CMV are chronically infected for years, but the duration of CMV urinary excretion is not associated with abnormalities of growth, or neurodevelopmental deficits. However, SNHL and progressive SNHL were associated with a shorter duration of CMV excretion.

Timing of perinatal human immunodeficiency virus type 1 infection and rate of neurodevelopment

BACKGROUND Identifying HIV-1-infected children who are at greatest risk for disease-related morbidities is critical for optimal therapeutic as well as preventive care. Several factors have been implicated in HIV-1 disease onset and severity, including maternal and infant host characteristics, viral phenotype and timing of HIV-1 infection. Early HIV-1 culture positivity, i.e. intrauterine infection, has been associated with poor immunologic, virologic and clinical outcomes in children of HIV-infected women. However, a direct effect of timing of infection on neurodevelopmental outcome in infancy has not yet been identified. METHODS Serial neurodevelopmental assessments were performed with 114 infants vertically infected with HIV-1 in a multicenter natural history, longitudinal study. Median mental and motor scores were compared at three time points. Longitudinal regression analyses were used to evaluate the neurodevelopmental functioning of children with early positive cultures and those with late positive cultures. RESULTS Early infected infants scored significantly lower than late infected infants by 24 months of age and beyond on both mental (P = 0.05) and motor (P = 0.03) measures. Early HIV-1 infection was associated with a decline in estimated motor scores of 1 standard score point per month compared with 0.28 point in the late infected group (P < 0.02). Estimated mental scores of the early infected group declined 0.72 point/ month, whereas the average decline of the late infected group was 0.30 point/month (P < 0.13). CONCLUSION Early HIV-1 infection increases a childs risk for poor neurodevelopmental functioning within the first 30 months of life.

Cognitive and adaptive behavior profiles in Smith-Magenis syndrome.

ABSTRACT. Smith-Magenis syndrome (SMS) is a multiple congenital anomalies and mental retardation syndrome associated with an interstitial deletion of chromosome 17 band p11.2. The incidence of this microdeletion syndrome is estimated to be 1 in 25,000 individuals. Persons with SMS have a distinctive neurobehavioral phenotype that is characterized by aggressive and self-injurious behaviors and significant sleep disturbances. From December 1990 through September 1999, 58 persons with SMS were enrolled in a 5-day multidisciplinary clinical protocol. Developmental assessments consisting of cognitive level and adaptive behavior were completed in 57 persons. Most patients functioned in the mild-to-moderate range of mental retardation. In addition, we report that patients with SMS have low adaptive functioning with relative strengths in socialization and relative weakness in daily living skills. These data were analyzed in light of the molecular extent of the microdeletion within 17p11.2. We found that the level of cognitive and adaptive functioning does depend on deletion size, and that a small percentage of SMS patients have cognitive function in the borderline range.

Early neurodevelopmental markers predictive of mortality in infants infected with HIV-1.

One‐hundred and fifty‐seven vertically infected HIV‐1 positive infants (85 males, 72 females) underwent longitudinal assessment to determine whether early neurodevelopmental markers are useful predictors of mortality in those infants who survive to at least 4 months of age. Survival analysis methods were used to estimate time to death for quartiles of 4‐month scores (baseline) on the Bayley Scales of Infant Development (BSID). Cox proportional hazards progression was used to estimate relative hazard (RH, 95% CI) of death for BSID scores and potential confounders. Thirty infants with BSID scores at 4 months of age died during follow‐up. Survival analysis revealed greater mortality rates in infants with BSID (Mental Developmental Index and Psychomotor Developmental Index) scores in the lower quartile(p=0.004,p=0.036). Unadjusted univariate analyses revealed increased mortality associated with baseline CD4+ 29%, gestational age <37 weeks, smaller head circumference, advanced HIV and higher plasma viral load. BSID scores independently predicted mortality after adjusting for treatment, clinical category, gestational age, plasma viral load and CD4+ percentage.

The Effect of Prenatal Drug Exposure and Caregiving Context on Children’s Performance on a Task of Sustained Visual Attention

Objectives: Three groups of children from low-income, urban environments were examined to determine the effects of prenatal drug exposure (PDE) and caregiving environment on sustained visual attention (SVA) at 7 years of age. Methods: Drug-exposed children remaining in maternal care (n = 43), drug-exposed children placed in nonmaternal care (n = 45), and community comparison (CC) children (n = 56) were administered a battery of neurocognitive tests, including the Conners’ Continuous Performance Test (CPT). Results: PDE children remaining in maternal care displayed more omission errors than CC children. PDE children in nonmaternal care had intermediate scores that did not differ significantly from PDE children in maternal care or CC children. There were no group differences with respect to commission errors or reaction time. CPT errors of omission and commission were significantly correlated with parent-reported attention problems and academic achievement scores. Conclusions: PDE in the context of care provided by a maternal caregiver with persistent drug use patterns may contribute to problems in children’s SVA at school-age. As parental drug abuse can interfere with the provision of early care, children raised in a drug-using context may be highly vulnerable to problems with self-regulation, including sustained attention. SVA problems may contribute to subsequent academic and behavioral problems as demands for concentration and sustained effort increase throughout childhood. Children who have been prenatally exposed to drugs or raised in a drug-using household may benefit from early intervention services to avoid problems in SVA that may interfere with subsequent neurocognitive functioning and academic performance.

Stimulant medications decrease energy expenditure and physical activity in children with attention-deficit/hyperactivity disorder

Abstract Objective: To determine the effect of stimulant medications used to treat children with attention-deficit/hyperactivity disorder (AD/HD) on energy expenditure, fuel utilization, and physical activity. Study design: Energy expenditure and physical activity were measured, respectively, by room respiration calorimetry and microwave motion detectors in 31 children with AD/HD (26 boys and 5 girls; ages 6 to 12 years) both while they were receiving their prescribed stimulant medication and after the medication had been discontinued for at least 24 hours. Fuel utilization was calculated from calorimetry data. Results: Total and awake energy expenditure including energy expended while doing schoolwork, riding a stationary bicycle, resting, and watching a movie were from 4% to 8% lower when the children were receiving their prescribed stimulant medication. Total and awake activity were also lower while they were receiving medication (16% to 22%) and accounted for the lower rates of energy expenditure. Sleeping metabolic rate, basal metabolic rate, and fuel utilization were unaffected by medication. Conclusions: Stimulant medications decrease physical activity, and hence, decrease the activity component of total daily energy expenditure in children with AD/HD. (J Pediatr 1999;135:203-7)

Neuropsychological and Neurobehavioral Sequelae Associated with Pediatric HIV Infection

Neuropsychological and neurobehavioral dysfunctions in infancy and childhood, resulting from human immunodeficiency virus (HIV) infection, warrant distinct consideration in a handbook of this nature. This merit stems from the unique impact of this disease process on the rapidly maturing central nervous system (CNS) of the child (Epstein et al., 1986; Falloon, Eddy, Wiener, & Pizzo, 1989; Pizzo & Wilfert, 1994) in conjunction with the historical scientific and clinical purview of neuro-psychology as the study of brain-behavior relationships (Lezak, 1995).

Differences in neuropsychological performance associated with ethnicity in children with HIV-1 infection: preliminary findings.

This study investigated the relationship between ethnicity (African American and European American) and neuropsychological performance in two specific neuropsychological domains (language and speed of information processing) in a group of HIV-1+ children. The Expressive One-Word Picture Vocabulary Test-Revised and the Rapid Color Naming subtest of the Comprehensive Test of Phonological Processing were administered to 5- to 7-year-old children (n = 22) as part of a comprehensive research or clinical protocol. African American children scored lower than European American children (p < .05) on both procedures. The observed performance difference emerged despite the fact that there were no group differences in age, immunologic clinical categories, intellect, level of maternal education, or CD4+ percentage and after using stringent exclusionary criteria, including history of enrollment in special education services and the presence of other chronic medical conditions. The implications of such findings are discussed within biological and demographic frameworks.

Effects of test administration order on children's neuropsychological performance: emerging one-word expressive and receptive language skills.

Differences in neuropsychological performance associated with specific test presentation sequences have been reported in adults. However, these effects have received little attention in children. The EOWPVT-R, a measure of one-word expressive language, and the PPVT-R, a measure of receptive language, were administered to 6- to 14-year-olds (control [n = 17] and experimental [n = 22] groups) in a counterbalanced fashion to investigate the potential effects of test presentation sequence on neuropsychological performance. Group findings were not evidenced subsequent to variation in test administration sequence. In contrast, order of test presentation revealed differences in performance. Administration of the PPVT-R prior to the EOWPVT-R resulted in enhanced EOWPVT-R expressive language scores in both groups of participants. Presentation of the PPVT-R after the EOWPVT-R did not affect performance. Applied and theoretical implications associated with these findings are discussed.

Effects of Polymorphisms of Chemokine Receptors on Neurodevelopment and the Onset of Encephalopathy in Children with Perinatal HIV-1 Infection

This study examined the effects of chemokine receptor polymorphisms on neurodevelopment and the onset of encephalopathy in children with perinatal HIV-1 infection. Infected children (N = 121) between the ages of 1 and 72 months were categorized into dichotomous groups (heterozygous or homozygous mutant vs. homozygous wild type) for each chemokine receptor 2 (CCR2) and chemokine receptor 5 (CCR5) allele. Neurodevelopmental measures included the Bayley Scales of Infant Development (BSID) for children age equal to or less than 30 months and the McCarthy Scales of Childrens Abilities (MSCA) for children aged > 30 months. A basic linear spline was used to model the mean value at each visit for the relevant test index, with determination of the slope between 4-12 months, 12-30 months, and 31-72 months of age. A mixed model analysis of variance was used to compare differences between slopes (Δβ) and intercepts (Δα) according to the presence or absence of the specified CCR2 or CCR5 polymorphism. Survival analyses were used to compare the onset of encephalopathy by chemokine receptor allelic grouping. After adjusting for potential confounds, statistically significant differences emerged in CCR5-39353, 39356, and 39402. Although the protective effects appeared to be discrete and transient, children with mutant CCR5 genotypes exhibited better neurodevelopmental outcomes than children with the wild type alleles. Chemokine polymorphisms did not appear to impact the onset of encephalopathy. Although possibly a temporary effect, HIV-1 infected children with selected mutant chemokine receptor polymorphims CCR5-39353, 39356, and 39402 may exhibit better neurodevelopmental outcome than children with the wild type allele.