Neuroimaging abnormalities in adults with sickle cell anemia: associations with cognition.

OBJECTIVE: This study was conducted to determine the relationship of frontal lobe cortical thickness and basal ganglia volumes to measures of cognition in adults with sickle cell anemia (SCA). METHODS: Participants included 120 adults with SCA with no history of neurologic dysfunction and 33 healthy controls (HCs). Participants were enrolled at 12 medical center sites, and raters were blinded to diagnostic group. We hypothesized that individuals with SCA would exhibit reductions in frontal lobe cortex thickness and reduced basal ganglia and thalamus volumes compared with HCs and that these structural brain abnormalities would be associated with measures of cognitive functioning (Wechsler Adult Intelligence Scale, 3rd edition). RESULTS: After adjusting for age, sex, education level, and intracranial volume, participants with SCA exhibited thinner frontal lobe cortex (t = -2.99, p = 0.003) and reduced basal ganglia and thalamus volumes compared with HCs (t = -3.95, p < 0.001). Reduced volume of the basal ganglia and thalamus was significantly associated with lower Performance IQ (model estimate = 3.75, p = 0.004) as well as lower Perceptual Organization (model estimate = 1.44, p = 0.007) and Working Memory scores (model estimate = 1.37, p = 0.015). Frontal lobe cortex thickness was not significantly associated with any cognitive measures. CONCLUSIONS: Our findings suggest that basal ganglia and thalamus abnormalities may represent a particularly salient contributor to cognitive dysfunction in adults with SCA.

Neuropsychologic performance in school-aged children with sickle cell disease: a report from the Cooperative Study of Sickle Cell Disease.

OBJECTIVES: To compare the results of serial neuropsychologic testing in children with sickle cell disease with the results of serial magnetic resonance imaging (MRI) examinations, particularly to evaluate neuropsychologic function in the absence of overt stroke. STUDY DESIGN: In the Cooperative Study of Sickle Cell Disease, serial neuropsychologic and MRI tests were performed in 373 patients (255 with hemoglobin SS and 118 with hemoglobin SC), 6 to 18 years of age. MRI of the brain and a neuropsychologic battery that included the Wechsler Intelligence Scale for Children (WISC-R or WISC-III) and the Woodcock-Johnson Math and Reading Achievement Tests were performed concurrently and repeated every 2 to 3 years. A silent infarct was defined as an MRI finding of increased signal intensity on T(2) imaging in a patient without a history of stroke. RESULTS: Twenty-seven patients, all with hemoglobin SS, had overt strokes and 62 had silent infarcts (52 with hemoglobin SS). Patients with hemoglobin SS and silent infarcts had significantly lower scores for math and reading achievement, Full-Scale IQ, Verbal IQ, and Performance IQ, when compared with those with normal MRI findings. In children with hemoglobin SS and normal MRI findings, the scores for Verbal IQ, math achievement, and coding (a subscale of Performance IQ) declined with increasing age. CONCLUSIONS: School-aged children with sickle cell disease had compromised neuropsychologic function in the presence of silent infarcts. In addition, they had declines in performance in certain areas of function over time. Therapeutic interventions that prevent or lessen cognitive impairment are needed before school entry for children with sickle cell disease.

Acute and long-term neurodevelopmental outcomes in children following bone marrow transplantation.

Bone marrow transplantation offers a potential cure for a number of childhood cancers, sickle cell anemia, and stabilization of a deteriorating and debilitating process in a number of metabolic disorders and leukodystrophies. Depending upon the disease, treatment prior to BMT, and natural history of the disease, BMT may increase the risk of neuropsychological toxicity for children undergoing BMT, or may actually improve their long-term neurodevelopmental outlook. The role of factors such as pre-BMT therapy, age at time of treatment, presence or absence of total body irradiation, and toxicities associated with GVHD are presented for consideration. A developmental model for understanding the emergence of neurocognitive effects of BMT is reviewed, and strategies for intervention are considered.

The prenatal visit.

In their role as advocates for children and families, pediatricians are in an excellent position to support and guide parents during the prenatal period. Prenatal visits allow the pediatrician to gather basic information from parents, provide information and advice to them, and identify high-risk situations in which parents may need to be referred to appropriate resources for help. In addition, prenatal visits are the first step in establishing a relationship between the pediatrician and parents and help parents develop parenting skills. The prenatal visit may take several possible forms depending on the experience and preferences of the parents, competence and availability of the pediatrician, and provisions of the health care plan.

Brief report: relationship between HIV infection and WPPSI-R performance in preschool-age children.

OBJECTIVE: To determine the neurodevelopmental effects of perinatally acquired HIV infection on children of preschool age. METHODS: Participants included 40 children infected with HIV between the ages of three and five and an equal number of noninfected controls individually matched according to ethnicity, age, sex, and prenatal drug exposure. Participants were administered the Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R), upon which an analysis of subtest distribution was conducted. RESULTS: Whereas both groups evidenced mean IQ and subtest scores significantly below published norms, an effect for HIV group status was not found when a factor combining Performance IQ (PIQ) and Verbal IQ (VIQ) was analyzed. However, the group infected with HIV scored significantly lower than controls on the Block Design subtest. CONCLUSIONS: Gross cognitive deficits are not evident among preschool children infected with HIV relative to matched controls. However, this study does provides some evidence for more focal deficits. Further investigation with older children should be conducted.

Family functioning, neurocognitive functioning, and behavior problems in children with sickle cell disease.

OBJECTIVE: To investigate the independent and combined contributions of neurocognitive and family functioning to mother-reported behavior problems in children with sickle cell disease (SCD) and evaluate the factor structure of the Family Environment Scale (FES) with African American families. METHOD: The study sample included 289 children enrolled in the multisite Cooperative Study of Sickle Cell Disease. The study protocol included neuropsychological evaluation and brain magnetic resonance imaging (MRI) of the children, and mothers completed the Child Behavior Checklist and Family Environment Scale. RESULTS: With child and maternal demographic parameters controlled, conflicted family functioning, but not neurocognitive functioning, accounted for a significant portion of the variance in mother-reported behavior problems. The factor structure of the FES for families of children with SCD was found to be similar to that for other families. CONCLUSIONS: Family functioning may be a salient target for fostering adaptation to chronic childhood illness.

The Outpatient Developmental Services Project: integration of pediatric psychology with primary medical care for children infected with HIV.

OBJECTIVE: To present a model in which pediatric psychology services are programmatically integrated into the primary care of children seen in a special immunology program. The program centers around serial neurodevelopmental/neuropsychological evaluation of children infected with HIV. METHOD: We describe the population served and the particular services provided, with specific focus on how the program was developed. We include a discussion of the barriers to service provision that have been encountered and the strategies employed to overcome these challenges. CONCLUSIONS: This approach, while not ideal, serves as a good example of how pediatric psychology can merge with primary medical care to maximize the benefits of both specialties for a patient population that is underserved in many respects.

The Miami pediatric quality of life questionnaire: parent scale.

Because there were limited measures available to assess health-related quality of life (HRQL) in children with chronic illnesses, this study was initiated to develop an empirically derived questionnaire for use in evaluating HRQL issues in children treated for cancer. Extensive interviews were conducted with 30 families of children with cancer, 10 of pre-school age, 10 of school age and 10 of adolescent age. Responses were videotaped and transcribed, then categorized to develop a pool of 56 items, which were administered to 132 children with cancer and to their parents. This report focuses on parental responses to objective items and ratings of importance of each of these items. Three primary categories, Self-Competence, Emotional Stability and Social Competence, were identified, each of which had solid internal consistency, sensitivity and reliability across 1-month intervals. The measure demonstrated the ability to discriminate between children with different types of cancer, offers an alternative to measures relying on expert judgment to assess HRQL and may lead to greater inclusion of psychological and social concerns as primary factors in determining HRQL in children participating in clinical trials.

Pain and fear ratings: clinical implications of age and gender differences.

The study investigated the relationships among children's self-report of anticipatory pain and fear, physiological measures of distress, and previous medical experience in 62 outpatients during allergy skin testing. Younger (aged 3-7 years) and older (aged 8-12 years) children reported similar amounts of pain and fear. Girls reported more pain than boys. Older children and boys provided differential pain and fear ratings compared with younger children and girls. Younger children's self-report of distress was not related to any physiological measures, but older children's report of fear was significantly related to blood pressure. In girls, positive medical experience was correlated with less pain. The implications of these findings for the clinical measurement and intervention of children's distress during painful medical procedures are discussed.

Neuropsychologic functioning of survivors of childhood medulloblastoma randomized to receive conventional or reduced-dose craniospinal irradiation: a Pediatric Oncology Group study.

PURPOSE: The purpose of this study was to test the hypothesis that survivors of medulloblastoma who were younger at diagnosis and those who received standard-dose cranial irradiation (SRT) of 36 Gy would have a lower performance on standardized tests of cognitive function and achievement than children who were older and those treated with reduced-dose cranial irradiation (RRT) of 23.4 Gy. PATIENTS AND METHODS: Eligible patients had been treated on Pediatric Oncology Group (POG) study 8631 for low-risk medulloblastoma that randomized patients to receive RRT or SRT after surgical resection. Those who were alive and free of progressive disease 6.1 to 9.9 years from completion of treatment were eligible for this study. Of the 35 eligible patients, 22 patients (13 SRT, nine RRT) participated in a battery of tests that included intellectual and academic development as well as ratings of health-related quality of life. RESULTS: Patients were stratified by treatment group (SRT v RRT) and into younger (Y) and older (O) groups by the median age at diagnosis (8.85 years), which resulted in four groups that we hypothesized would show neuropsychologic test scores in the following order: Y/SRT less than Y/RRT less than O/SRT less than O/RRT. Evidence to support the hypothesized ordering of groups in terms of neuropsychologic toxicity was obtained with regard to Performance Intelligence Quotient (IQ), Full Scale IQ, Attention, Reading, and Arithmetic. CONCLUSION: Children treated for medulloblastoma experienced less severe neuropsychologic toxicity when treated with 23.4 Gy instead of 36 Gy cranial irradiation. Older children experienced less toxicity than children who were younger at the time of irradiation.

A firearm safety program for children: they just can't say no.

The purpose of this study was to compare children's play and aggressive behavior with firearms before and after an information-based intervention. Correlates of aggression and gun play were also analyzed. Subjects were 24 pairs of preschool children videotaped for 10 minutes in a structured play setting, in which they had access to a variety of toys and to real and toy guns. One child from each dyad was then exposed to an information-based intervention and told not to play with guns. The children were again videotaped in the same setting approximately 1 week later. Results indicated that the intervention was ineffective in modifying the behavior of the children. Regression analyses revealed that access to a parent's firearm was correlated with gun play and that gun play and handling of firearms in the home were correlated with aggressive behavior. The findings in this study represent the first systematic attempt to decrease gun play in children and suggest that information provision alone is an insufficient intervention.

Cognitive functioning and brain magnetic resonance imaging in children with sickle Cell disease. Neuropsychology Committee of the Cooperative Study of Sickle Cell Disease.

OBJECTIVE: Brain magnetic resonance imaging (MRI) and neuropsychological evaluations were conducted to determine whether neuroradiographic evidence of infarct in children with sickle cell disease between ages 6 and 12 years would result in impairment in cognitive and academic functioning. METHOD AND DESIGN: Children enrolled in the Cooperative Study of Sickle Cell Disease were evaluated with brain MRI and neuropsychological evaluation. Completed studies were obtained for 194 children, 135 with HbSS. MRIs were categorized according to the presence of T2-weighted, high-intensity images suggestive of infarct and were further categorized on the basis of a clinical history of cerebrovascular accident (CVA). An abnormal MRI but no clinical history of CVA was classified as a silent infarct. Neuropsychological evaluations included assessment of both global intellectual functioning and specific academic and neuropsychological functions. RESULTS: Central nervous system (CNS) abnormalities were identified on MRI in 17.9% of the children (22.2% of children homozygous for HbS), and a clinical history of CVA (N = 9, 4.6%) was identified in only children with HbSS disease. Subsequent analyses examined only children with HbSS. Children with a history of CVA performed significantly poorer than children with silent infarcts or no MRI abnormality on most neuropsychological evaluation measures. Children with silent infarcts on MRI performed significantly poorer than children with no MRI abnormality on tests of arithmetic, vocabulary, and visual motor speed and coordination. CONCLUSIONS: These results substantiate the importance of careful evaluation, educational planning, and medical intervention for CNS-related complications in children with sickle cell disease.

The effects of HIV on cognitive and motor development in children born to HIV-seropositive women with no reported drug use: birth to 24 months.

OBJECTIVE: This study documents delays in the mental and motor functioning of infants perinatally infected with human immunodeficiency virus (HIV) while controlling for confounding effects of prenatal drug exposure, ethnicity, socioeconomic status, and maternal separation and death. METHODS: The cognitive and motor development of 126 infants born to nondrug-using, HIV-seropositive Haitian women was assessed at 3-month intervals through 24 months of age using the Bayley Scales of Infant Development. By 18 months of age, 28 of the infants were diagnosed as HIV-infected, and the 98 uninfected infants served as a control group. The infected and uninfected infants did not differ with respect to mean gestational age, birth weight, ethnicity, or rates of maternal separation and death. RESULTS: By 3 months of age, the mean mental and motor scores of the infected infants were significantly lower than those of the uninfected controls. Furthermore, the initial differences between the two groups increased over time, as many of the infected infants became increasingly delayed. Although the infected infants tended to perform more poorly than the uninfected infants, nearly one third of the infected infants exhibited relatively normal cognitive development and half demonstrated relatively normal motor development. CONCLUSIONS: Over the first 24 months of life, the mean rate of development of HIV-infected infants is significantly slower than that of noninfected infants born to seropositive mothers. This occurs even when the effects are not confounded with those of prenatal drug exposure.

Hospitalizations for painful episodes: association with school absenteeism and academic performance in children and adolescents with sickle cell anemia.

Painful episodes have been identified as one of the most frequent manifestations of sickle cell anemia (hemoglobin HbSS). This retrospective study compared the frequency of hospitalization and the academic performance of two groups of children with HbSS (ages 8 to 18 years) with differing frequencies of pain. A high frequency (HF) group (n = 10) was composed of children who had four or more hospitalizations for pain in the study period; those in the low frequency (LF) group (n = 11) had one or no hospitalizations for pain during the study period. The two groups were matched on age (within 6 months), gender, and ethnicity. Standardized assessments of academic achievement and school records of attendance and class grades were obtained for all participants. The standardized academic achievement for both groups was approximately one standard deviation below the normative mean of the population sample, and class grades were below a C average. School absence was frequent in both groups (LF mean = 16.8 days/year; HF mean = 35.4 days/year), and children in the HF group had significantly more absences than children in the LF group. The lack of difference in academic performance between the two groups suggests that there may be factors other than school absenteeism that affect academic achievement, which require further investigation.

Interpersonal distance and coping in children with HIV and cancer.

We compared interpersonal distance and coping among two groups of pre-school pediatric patients diagnosed with either HIV or cancer and a third group of healthy children. In comparison to the children with cancer, children with HIV indicated greater mother-child interpersonal distance--a finding that correlated with mothers' reports of social withdrawal. Other notable findings included increased father-child distance in the HIV population and mother-child discrepancies of perceived interpersonal distance. In addition, seven of the children with HIV indicated that the adults turn away--a finding that correlated with the children's knowledge of their illness. We also explored the possible role of protective communication in the pediatric HIV population.

Coping and communication among parents and children with human immunodeficiency virus and cancer.

Coping strategies and communication of three groups of 20 preschool children and their parents were compared. One group was composed of children infected with the human immunodeficiency virus (HIV) who displayed clinical symptoms of the disease; the second group was composed of children diagnosed with cancer; and the third group was composed of healthy children. Results indicated that the parents of children with life-threatening illnesses reported greater degrees of wishful thinking than did control subjects. Furthermore, parents of children with HIV reported more wishful thinking than did parents of children with cancer. Finally, significantly more children with cancer were aware of their diagnosis than were children with HIV. The findings in this study suggest coping and communication difficulties for parents and children with HIV.

Differential medication of child versus adult postoperative patients: the effect of nurses' assumptions.

We examined nurses' assumptions concerning children and analgesia that have been hypothesized to explain the differential medication of postoperative child and adult patients. One hundred fourteen nurses from various pediatric and adult inpatient units of a large, urban teaching hospital were included in the study. A questionnaire consisting of four vignettes describing two hypothetical postoperative situations involving a child and adult patient, questions concerning choice of analgesic and assessment of pain for the hypothetical patients, and questions concerning the nurses' assumptions about children and analgesia was distributed to each nurse. The findings illustrate a pattern of differential medication of hypothetical child relative to hypothetical adult postoperative patients. The belief that children feel less pain than adults and concern about respiratory depression were associated with nurses' analgesia decisions.

Enhanced parenting knowledge and skills in mothers of preschool children with sickle cell disease.

Compared 25 preschool children with sickle cell disease (SCD) to demographically matched healthy comparison children on maternal reports of child-rearing beliefs and practices and maternal and child behaviors related to social adjustment. Mothers of children with SCD possessed significantly more knowledge of appropriate discipline techniques. The groups did not differ on maternal reports of socially relevant child behavior. However, when mother-child interactions were observed in free play and structured play settings, mothers of children with SCD treated their children as competent significantly more, and treated their children as incompetent significantly less, than comparison mothers. Mothers of children with SCD also used significantly more reinforcement during the final toy pick-up condition. There were no observed differences between groups in the children's behavior.