An analysis of select emerging executive skills in perinatally HIV-1-infected children.

This study examined the effect of perinatal HIV-1 infection on emerging executive skills in children (n = 161) ages 8 to 12 years. HIV-positive (n = 76) and HIV-negative (n = 85) children were eligible to participate. The HIV-positive children included those who had experienced a CDC Class C event (greater severity, n = 22) and those who were HIV-positive but who had not experienced a CDC Class C event (less severity, n = 54). Measures of emerging executive functions completed by the children included subtests from the Developmental Neuropsychological Assessment (NEPSY), the Trail-Making Test-Part B, and a subtest from the Woodcock-Johnson Battery-Revised. Ratings of executive functions were obtained from caretakers using the Behavior Rating Inventory of Executive Functions. Generalized estimating equations methods, discriminate analyses, and global deficit score analyses were performed to determine whether differences emerged between the three clinical groups while using strict controls. The present results revealed significant group differences in unadjusted mean scores measuring executive functioning. However, such differences did not remain statistically significant when moderating variables were taken into consideration in the models. The apparent deficit in executive functioning for the HIV-positive children was found to be largely due to differential psychosocial and environmental factors rather than HIV disease and its severity, and in this cohort, the effects of HIV-1 infection on emerging executive functions appeared to be negligible when controlling for treatment and moderating psychosocial variables.

Effects of perinatal HIV infection and associated risk factors on cognitive development among young children.

OBJECTIVE: We examined the effect of HIV, in combination with other important health and social factors, on the development of cognitive abilities of children perinatally exposed to HIV. METHODS: Serial cognitive assessments were performed for 117 children who were infected vertically and 422 children who were exposed to but not infected with HIV, in a multicenter, natural history, longitudinal study. Repeated-measures analyses were used to evaluate the neurocognitive development of children between the ages of 3 and 7 years, as measured by the McCarthy Scales of Children's Abilities (MSCA). RESULTS: Children with HIV infection and class C status scored significantly lower in all domains of cognitive development, across all time points, than did those who were HIV infected without an AIDS-defining illness and those who were HIV exposed but not infected. There were no significant differences between the 2 latter groups in General Cognitive Index or specific domain scores. Rates of change in cognitive development were comparable (parallel) among all 3 groups over a period of 4 years. Factors that were associated consistently and significantly with lower mean scores were HIV status, number of times an examination had been completed previously, primary language, maternal education, and gender. No factors were related to rate of change of any mean domain score. CONCLUSIONS: An early AIDS-defining illness increased the risk of chronic static encephalopathy during the preschool and early school age years. Children with HIV infection but no class C event performed as well as noninfected children in measures of general cognitive ability. No significantly different profiles of strengths and weaknesses for verbal, perceptual-performance, quantitative, or memory functioning were observed among children with or without HIV infection. A number of factors were found to have significant effects on the mean scores of children in all 3 groups; however, they were not related to the rate at which learning occurred.

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 I 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 < or = 30 months and the McCarthy Scales of Children's 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 (AP) and intercepts (AX) 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.

Sleep-disordered breathing symptoms are associated with poorer cognitive function in 5-year-old children.

OBJECTIVE: To assess the relation of sleep-disordered breathing (SDB) symptoms in children to neurocognitive function. STUDY DESIGN: A cross-sectional, population-based study of 205 5-year-old children. A parent-completed questionnaire was used to ascertain SDB symptoms, defined as frequent snoring, loud or noisy breathing during sleep, or witnessed sleep apnea. Polysomnography (PSG) data were available in 85% of children. Standardized neurocognitive tests were administered by a trained psychometrist unaware of the children's SDB status. Children with (n=61) and without SDB symptoms were compared using analysis of variance to adjust for demographic and respiratory health variables. RESULTS: Children with SDB symptoms scored significantly lower than those without SDB symptoms on tests of executive function (95.5 vs 99.9 on NEPSY Attention/Executive Core Domain, P=.02; 10.4 vs 11.2 on Wechsler Preschool and Primary Scale of Intelligence, Revised [WPPSI-R] Animal Pegs test, P=.03), memory (96.8 vs 103.0 on NEPSY Memory Domain, P=.02), and general intellectual ability (105.9 vs 111.7 on WPPSI-R Full Scale IQ, P=.02). There were no significant differences on a computerized continuous performance task. These findings persisted when children with PSG evidence of obstructive sleep apnea (OSA) were excluded from analysis. CONCLUSION: Even in the absence of OSA, SDB symptoms are associated with poorer executive function and memory skills and lower general intelligence in 5-year-old children.

Symptoms of sleep-disordered breathing in 5-year-old children are associated with sleepiness and problem behaviors.

OBJECTIVE: Sleep-disordered breathing (SDB) in children is reportedly associated with problem behaviors suggestive of attention-deficit/hyperactivity disorder; however, there are few data on the relation of SDB to problem behaviors in the general pediatric population. The goal of this study was to assess the prevalence of SDB symptoms in 5-year-old children and their relation to sleepiness and problem behaviors. METHODS: A population-based, cross-sectional survey was conducted of a birth cohort of children who were born in eastern Massachusetts. Subjects were 3019 5-year-old children (1551 boys, 1468 girls) who were enrolled in the Infant Care Practices Study and whose mothers were contacted within 3 months of their child's fifth birthday. A parent-completed questionnaire was used to ascertain the presence and intensity of snoring and other SDB symptoms and the presence of daytime sleepiness and problem behaviors. Parent-reported hyperactivity, inattention, and aggressiveness were each assessed by a single question that was validated against the Conners' Parent Rating Scale. SDB was defined as frequent or loud snoring; trouble breathing or loud, noisy breathing during sleep; or witnessed sleep apnea. RESULTS: Parent-reported hyperactivity (19%) and inattention (18%) were common, with aggressiveness (12%) and daytime sleepiness (10%) reported somewhat less often. SDB symptoms were present in 744 (25%) children. Compared with children without snoring or other symptoms of SDB, children with SDB symptoms were significantly more likely to have parent-reported daytime sleepiness (odds ratio [OR]: 2.2; 95% confidence interval [CI]: 1.7-2.8) and problem behaviors, including hyperactivity (OR: 2.5; CI: 2.0-3.0), inattention (OR: 2.1; 95% CI: 1.7-2.6), and aggressiveness (OR: 2.1; 95% CI: 1.6-2.6). These associations remained significant after adjustment for sex, race/ethnicity, maternal education level, maternal marital status, household income, and respiratory health history. CONCLUSIONS: SDB symptoms are common in 5-year-old children and are associated with an increased risk of daytime sleepiness and with problem behaviors suggestive of attention-deficit/hyperactivity disorder.

High rates of behavioral problems in perinatally HIV-infected children are not linked to HIV disease.

OBJECTIVE: Descriptive studies and clinical reports have suggested that human immunodeficiency virus (HIV)-positive children are at risk for behavioral problems. Inadequate control groups and sample sizes have limited the ability of investigators to consider multiple influences that place HIV-positive children at risk for poor behavioral outcomes. We examined the unique and combined influences of HIV, prenatal drug exposure, and environmental factors on behavior in children who were perinatally exposed to HIV. METHODS: Participants included 307 children who were born to HIV-positive mothers (96 HIV infected and 211 seroreverters) and enrolled in a natural history, longitudinal study of women to infant HIV transmission. Caregivers completed parent behavioral rating scales, beginning when the children were 3 years old. Data were also collected on prenatal drug exposure; child age, gender, and ethnicity; caregiver relationship to child; and birth complications. RESULTS: Multivariate analyses comparing the HIV-infected children with perinatally exposed but uninfected children from similar backgrounds failed to find an association between either HIV status or prenatal drug exposure and poor behavioral outcomes. The strongest correlates of increased behavioral symptoms were demographic characteristics. CONCLUSIONS: This study suggests that although a high prevalence of behavioral problems does exist among HIV-infected children, neither HIV infection nor prenatal drug exposure is the underlying cause. Rather, other biological and environmental factors are likely contributors toward poor behavioral outcomes.