Cynthia Chase

Early Cognitive and Motor Development Among Infants Born to Women Infected With Human Immunodeficiency Virus

Objective. To examine the frequency, timing, and factors associated with abnormal cognitive and motor development during the first 30 months of life in infants born to women infected with human immunodeficiency virus type 1 (HIV-1). Methods. Serial neurodevelopmental assessment was performed with 595 infants born to women infected with HIV-1 in a multicenter, prospective, natural history cohort study. Survival analysis methods were used to evaluate 6 outcome events related to abnormal cognitive and motor growth (time to confirmed drop of 1 SD, time to first score <69, and time to confirmed drop of 2 SD) in Bayley Scales of Infant Development Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) scores among infected (n = 114) and uninfected (n = 481) infants. Proportional hazards modeling was used to evaluate the effects of HIV infection status, prematurity, prenatal exposure to illicit drugs, maternal educational attainment, and primary language. Results. HIV-1 infection was significantly associated with increased risk for all outcome events related to abnormal mental and motor growth. Differences between infected and uninfected infants were apparent by 4 months of age. Prematurity was associated with increased risk for MDI <69 and PDI <69. Maternal education of <9 completed years was associated with increased risk for MDI <69. Neither prenatal exposure to illicit drugs nor primary language other than English was associated with abnormal development. Conclusion. A significant proportion of infants with HIV-1 infection show early and marked cognitive and motor delays or declines that may be important early indicators of HIV disease progression. These abnormalities are independent of other risk factors for developmental delay.

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.

Head growth and neurodevelopment of infants born to HIV-1–infected drug-using women

Objective: To describe neurodevelopment and head growth in HIV-1–infected and exposed uninfected infants with and without in utero exposure to opiates and cocaine. Methods: Using data from a multicenter cohort study of HIV-1–infected women and their children, the authors fit repeated measures regression models to estimate the effects of HIV-1 infection and in utero hard drug exposure on head circumference and Bayley Scales of Infant Development standard scores during the first 30 months. Results: Of the 1,094 infants included in the analysis, 147 (13%) were HIV-1–positive and 383 (35%) were exposed in utero to opiates or cocaine (drug-positive). Mean 4- month Bayley mental scores were lower in infants with only HIV-1 positivity (HIV-positive and drug-negative) (-8.2 points, p < 0.0001) or only drug exposure (HIV-negative and drug-positive) (−4.4 points, p = 0.0001) and tended to be lower in infants with both factors (HIV-positive and drug-positive) (−3.7 points, p = 0.0596), compared with those who were HIV-1-negative and not drug exposed (HIV-negative and drug-negative). However, by 24 months of age, there was no longer a decrement among HIV-negative and drug-positive infants, whereas HIV-1 infection was still associated with a decrement relative to uninfected infants. Similar results were seen for Bayley motor scores and for head circumference Z scores. Conclusions: HIV-1 infection and in utero opiate and cocaine exposure decrease birth head circumference and slow neurodevelopment at 4 months. At 24 months of age, however, only HIV-1 infection is associated with decreased neurodevelopment and head circumference. There may be some postnatal recovery from the effects of in utero hard drug exposure. Importantly, the detrimental effects of HIV-1 positivity and maternal hard drug use on neurodevelopment at 4 months are not additive, although they are additive for birth head circumference.

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.