Neurologic, neurocognitive, and brain growth outcomes in human immunodeficiency virus-infected children receiving different nucleoside antiretroviral regimens. Pediatric AIDS Clinical Trials Group 152 Study Team.

OBJECTIVES: To compare the impact of three different nucleoside reverse transcriptase inhibitor regimens, zidovudine (ZDV) monotherapy, didanosine (ddI) monotherapy, and ZDV plus ddI combination therapy, on central nervous system (CNS) outcomes in symptomatic human immunodeficiency virus (HIV)-infected children. METHODS: Serial neurologic examinations, neurocognitive tests, and brain growth assessments (head circumference measurements and head computed tomography or magnetic resonance imaging studies) were performed in 831 infants and children who participated in a randomized double-blind clinical trial of nucleoside reverse transcriptase inhibitors. The Pediatric AIDS Clinical Trials Group study 152 conducted between 1991 and 1995 enrolled antiretroviral therapy-naive children. Subjects were stratified by age (3 to <30 months of age or 30 months to 18 years of age) and randomized in equal proportions to the three treatment groups. RESULTS: Combination ZDV and ddI therapy was superior to either ZDV or ddI monotherapy for most of the CNS outcomes evaluated. Treatment differences were observed within both age strata. ZDV monotherapy showed a modest statistically significant improvement in cognitive performance compared with ddI monotherapy during the initial 24 weeks, but for subsequent protection against CNS deterioration no clear difference was observed between the two monotherapy arms. CONCLUSIONS: Combination therapy with ZDV and ddI was more effective than either of the two monotherapies against CNS manifestations of human immunodeficiency virus disease. The results of this study did not indicate a long-term beneficial effect for ZDV monotherapy compared with ddI monotherapy.

Clinical and laboratory characteristics of a large cohort of symptomatic, human immunodeficiency virus-infected infants and children. AIDS Clinical Trials Group Protocol 152 Study Team.

BACKGROUND: A large cohort of antiretroviral therapy-naive, symptomatic, HIV-infected children were enrolled into a controlled therapeutic trial (AIDS Clinical Trials Group Protocol 152), providing an opportunity to describe their clinical and laboratory characteristics and determine age-related distinctions. METHODS: Study entry evaluations for 838 of 839 enrolled children were analyzed. Weight, head circumference (if < 30 months of age), neuroradiologic imaging of the head, developmental or cognitive status and neurologic examination were assessed. Laboratory studies included hemoglobin, absolute neutrophil count, CD4 cell count, serum amylase, alanine aminotransaminase, p24 antigen and HIV blood culture. Data were categorized by age (3 to < 12 months, 12 to < 30 months, 30 months to 6 years and > or = 6 years). RESULTS: Younger children had significantly higher rates of abnormalities before antiretroviral therapy, especially factors relating to growth and neurologic or cognitive function. Lower CD4+ cell counts and percentages as well as a positive serum p24 antigen correlated with lower weight-for-age Z scores and developmental indices. CONCLUSIONS: These data provide a description of the clinical characteristics of HIV-infected US children at the time antiretroviral therapy is initiated for HIV-related symptoms. The high rate of abnormalities of growth, development and cognitive ability that were observed in children < 30 months of age demonstrates that treatment strategies should be developed for earlier intervention.

An exploratory study of the structure and validity of pediatric examination of educational readiness (PEER) factors.

The Pediatric Examination of Educational Readiness (PEER) is an assessment instrument specifically designed for use by pediatricians in assessing the development of preschool children. The present study investigated the psychometric properties of the PEER. Specifically, factor analyses of items from the Developmental Attainment and Associated Observation components of the test were performed. The PEER was administered to 69 preschool children. Three major factors were identified as making up the Developmental Attainment portion of the test: perceptual-motor, verbal-cognitive, and gross motor. The Associated Observations component was found to be composed of only one factor, attention. Children's performance on only two of these four factors was associated with their performance on the McCarthy Scales, the Woodcock-Johnson skills cluster, and the Minnesota Child Development Inventory. Discussion focused on the validity and utility of the PEER.

Nonhandicapped very-low-birth-weight infants at one year of age: developmental profile.

The developmental profile of 61 very-low-birth-weight infants without major cognitive, motor, or sensory deficits was compared with that of 28 term infants at 1 year chronologic age. The groups significantly differed in two ways on the Revised Gesell Developmental Schedules. First, very-low-birth-weight infants were more likely than term infants to have significant discrepancies between either their fine motor or language abilities and their early problem-solving skills as measured by the Adaptive scale of the Gesell. Second, across all fields of behavior (adaptive, gross motor, fine motor, language, and personal/social), very-low-birth-weight infants scored significantly below term infants. The very-low-birth-weight infant's motor performance significantly correlated with bronchopulmonary dysplasia, intracranial hemorrhage, and number of days spent in the hospital. Language performance significantly correlated with intracranial hemorrhage, birth weight, and sex. These findings underscore the limitations of global developmental scores to describe adequately the developmental performance of very-low-birth-weight infants. Instead, a comprehensive assessment of all fields of behavior is necessary to provide an accurate profile of this high-risk group.

Monoclonal antibody ELISA for cotinine in saliva and urine of active and passive smokers.

The value of a monoclonal antibody-based ELISA for measuring cotinine in saliva and urine of active and passive smokers was assessed. Cotinine (mean +/- SEM) was detected in all 26 saliva (392 +/- 74 ng/ml) and 27 urine (4264 +/- 508 ng/mg creatinine; 2566 +/- 364 ng/ml) samples from smoking parents, but in only two of 36 salivas and one of 37 urines from nonsmokers (P less than 0.001). Similarly, mean cotinine levels in 30 salivas (4.67 +/- 1.10 ng/ml) and 33 urines (35.5 +/- 8.8 ng/mg creatinine; 25.3 +/- 8.1 ng/ml) from passively exposed children were significantly higher (P less than 0.001) than in fluids of 36 unexposed children. Children's levels showed a strong correlation (P less than 0.001) with the number of cigarettes smoked in the home, but only when data from nonsmoking households were included in the analysis. In adult smokers there was a positive correlation between salivary and urinary cotinine (P = 0.002) and a close relationship between urinary cotinine and cigarettes smoked per day (P = 0.066). The ELISA gives a reliable quantitative measure of cotinine as an indicator of active and passive exposure to tobacco smoke. However, correlations with cotinine can be overestimated if large numbers of nonsmokers are included in the comparison.

Neurodevelopmental status of low birth weight infants with bronchopulmonary dysplasia requiring prolonged oxygen supplementation.

Fifty infants weighing 1,500 g or less at birth with a diagnosis of bronchopulmonary dysplasia (BPD) were followed to a mean age of 25 months to determine their clinical course and short-term neurodevelopmental outcome after discharge from the Neonatal Intensive Care Unit, and to identify possible predictive factors for outcome. Because study participation was voluntary, the subjects may not have represented the total population of BPD survivors. Occurrences of abnormalities were high: 11 hearing impaired, 10 legally blind, 14 cerebral palsy, and 23 abnormal development scores. Twenty-one subjects had feeding problems and weight was below the fifth percentile in 26. Home-oxygen therapy was required by 50 per cent of the subjects. Although severity of illness, duration of oxygen therapy and feeding problems were greater among those sent home on oxygen, their neurodevelopmental status did not differ from that of infants breathing room air by discharge. Factors associated with neurodevelopmental outcome were intracranial hemorrhage, pulmonary air leak, and length of hospital stay.

Factors affecting head growth and intellectual function in children of drug addicts.

The effect of maternal heroin and methadone use on head growth and neurodevelopmental performance was studied in preschool children of untreated heroin addicts (n = 25), women receiving methadone therapy (n = 26), and a drug-free comparison group (n = 41) who had been followed from birth. The mean birth head circumference of both groups of drug-exposed infants was significantly below that of the comparison group; however, the only factors determined by multiple regression analysis as associated with head size at birth were maternal nutritional status and birth weight. By preschool age, head size did not differ significantly among groups. The factors associated with postnatal head growth were birth weight, intrapartum risk score, and race. Data show an increased incidence of low-average and mildly retarded intellectual performance in the drug-exposed children. Regression analyses demonstrated that amount of prenatal care, prenatal risk score, and home environment were most predictive of intellectual performance and that the degree of maternal narcotic use was not a significant factor.

Fetal and postnatal growth of children born to narcotic-dependent women.

We studied the effect of heroin and methadone on birth length and 3-year stature of children of untreated heroin addicts (n = 22), women receiving methadone maintenance therapy (95% were polydrug users) (n = 21), and a drug-free comparison group (n = 28), after adjustment for biologic, demographic, and health variables. The mean birth lengths of both groups of drug-exposed infants were significantly below that of a comparison group; however, group means were similar after adjustment for sex, race, prenatal care, pregnancy weight gain, obstetrical risk, maternal education, and smoking. At 3 years of age the mean height was comparable for all groups. When adjusted for birth length, parental height, and smoking, the methadone group was significantly shorter than children exposed to heroin in utero, and the comparison group assumed an intermediate position. These data indicate that the effect of heroin and methadone on intrauterine growth cannot be differentiated from that of associated factors, and that postnatal growth of children exposed to narcotics during pregnancy is no more impaired than that of a high-risk comparison group. Children of all three groups deserve continued observation and efforts to improve their environment in order that their full potential might be achieved.