Marta H. Lifschitz

ZIDOVUDINE, DIDANOSINE, OR BOTH AS THE INITIAL TREATMENT FOR SYMPTOMATIC HIV-INFECTED CHILDREN

BACKGROUND Zidovudine has been the drug of choice for the initial treatment of symptomatic children infected with the human immunodeficiency virus (HIV). This trial was designed to assess the efficacy and safety of treatment with zidovudine alone as compared with either didanosine alone or combination therapy with zidovudine plus didanosine. METHODS In this multicenter, double-blind study, symptomatic HIV-infected children 3 months through 18 years of age were stratified according to age (<30 months or > or =30 months) and randomly assigned to receive zidovudine, didanosine, or zidovudine plus didanosine. The primary end point was length of time to death or to progression of HIV disease. RESULTS Of the 831 children who could be evaluated, 92 percent had never received antiretroviral therapy and 90 percent had acquired HIV perinatally. An interim analysis (median follow-up, 23 months) showed a significantly higher risk of HIV-disease progression or death in patients receiving zidovudine alone than in those receiving combination therapy (relative risk, 0.61; 95 percent confidence interval, 0.42 to 0.88; P=0.007). The study arm with zidovudine alone was stopped and unblinded; the other two treatment arms were continued. At the end of the study, didanosine alone had an efficacy similar to that of zidovudine plus didanosine (median follow-up, 32 months) (relative risk of disease progression or death, 0.98; 95 percent confidence interval, 0.70 to 1.37; P=0.91). A significantly lower risk of anemia or neutropenia was seen in patients receiving didanosine alone (P=0.036). CONCLUSIONS In symptomatic HIV-infected children, treatment with either didanosine alone or zidovudine plus didanosine was more effective than treatment with zidovudine alone. The efficacy of didanosine alone was similar to that of the combination therapy and was associated with less hematologic toxicity.

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. Childrens 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.

Clinical and laboratory characteristics of a large cohort of symptomatic, human immunodeficiency virus-infected infants and children

BackgroundA 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 disti

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.

Neurologic, Neurocognitive, and Brain Growth Outcomes in Human Immunodeficiency Virus-Infected Children Receiving Different Nucleoside Antiretroviral Regimens

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.

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. Childrens 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.

EFFECTS OF PASSIVE SMOKING ON CHILDREN'S BEHAVIORAL AND COGNITIVE DEVELOPMENT

Seventy children were evaluated at the mean age of 4.7 years as part of a longitudinal study of full term infants born to cigarette smokers and to non-smokers. They were enrolled at birth. Evaluation included a PEER [Pediatric Examination of Education Readiness]: (score: 1=no concern, 2=equivocal, 3=definite concern); McCarthy Scales, speech & learning assessment, and pulmonary function testing. Parents completed an ANSER System questionnaire: (0=definite concern, 1=equivocal, 2=no concern). The history of passive smoking was validated by measurment of cotinine in urine and saliva of the children and their mothers. Significant findings are shown in the table. Multiple regression analysis was used to adjust for sex, race, SES, preschool experience and urine cotinine level.These data indicate that exposure to smoking in utero or in childhood may affect neurobehavioral function of children.

66 THE DEVELOPMENTAL PROFILE OF THE NON-HANDICAPPED VERY LOW BIRTH WEIGHT (VLBW) INFANT AT 1 YEAR OF AGE

Information about general outcome of VLBW infants (i.e. those with retardation, C.P., blindness or deafness vs. those without major handicaps) is readily available. Yet, descriptions of the developmental profile of the non-handicapped VLBW infant are limited. Do VLBW infants without major handicaps exhibit uneven development at any early age? This question was addressed by studying 61 VLBW infants (followed prospectively to a mean age of 34 mo.) who met the following criteria: 1) normal cognitive functioning (group mean 92±19) 2) absence of major motor or sensory impairment 3) assessment on the Revised Gesell Developmental Schedule (GDS) at 1 year of age (mean chronologic age of 53±5 wks, mean corrected age 42±5 wks). Mean birth weight was 1082±221 gms; mean gestational age was 28.9±2 wks. The following is the developmental profile on the GDS (quotient of performance age ÷ corrected age):Both fine motor and language quotients were significantly lower than adaptive quotient (Students t test for matched pairs; t=8.35, 9.21; p<.001). 36 infants had ≥4 wk difference between fine motor and adaptive performance; for language performance, 32 had ≥4 wk difference. This study reveals that a majority of non-handicapped VLBW infants have significant deficits in fine motor and/or language skills at an early age. Longitudinal follow-up will reveal whether these weaknesses persist to school age, when such skills become major determinants of academic success.

RELATIONSHIP OF DEVELOPMENTAL OUTCOME TO ACQUISITION OF TERM MILESTONES AND TO IVH IN VLBW INFANTS

Thirty-eight VLBW infants were evaluated in terms of achievement of 5 milestones by 40 weeks post-conceptual age (PCA). These were the ability 1)to breathe without assistance, 2)to breathe room air, 3)to take total oral feedings, 4)to be free of apnea and/or bradycardia, and 5)to maintain stable body temperature in an open crib. Developmental performance was evaluated at 13 to 41 mos. using the Bayley Scales (MDI) or the McCarthy Scales (GCI). A significant difference with respect to outcome (p<.01) was found for patients achieving all milestones (Group A) versus those attaining 4 or fewer (Group B).The presence of & grade of IVH was also significantly related to outcome (p<.002). Significance was retained for both milestones (p<.05) & IVH(p<.01) when regressed together on outcome, but IVH did not affect milestone attainment(p<.25). When considering grade of IVH, SES, birth wt. & milestone attainment simultaneously, IVH became the single factor significantly related to outcome (p<.005). Thus, although there is a significant relationship between milestone achievement at 40 wks PCA & outcome, severity of IVH has the most significant association with performance.