ABSTRACT. Objectives. We characterized a population-based cohort of school-aged children with severe hemophilia with respect to type of treatment, on-demand versus prophylaxis, and frequency of bleeding episodes in the year before enrollment. We also investigated the association between hemophilia-related morbidity, measured by number of bleeding episodes in the year before enrollment, and academic performance after adjustment for other factors known to have an effect on achievement. Finally, we explored the mechanisms for the association between bleeding episodes and academic achievement.Study Design. This study was a multicenter investigation of boys 6 to 12 years old with severe factor VIII deficiency (clotting factor level <2%) receiving care in US hemophilia treatment centers. Children with a history of inhibitor, severe developmental disorder, significant psychiatric disorder, or insufficient fluency in English were excluded from the study. On-demand treatment was defined as administration of clotting factor on the occurrence of a bleeding episode. Prophylactic therapy was defined as a course of regular infusions for >2 months with a goal of preventing bleeding episodes. Academic achievement was measured by the Wechsler Individual Achievement Test. Quality of life was measured by the Child Health Questionnaire. Of particular interest was the Physical Summary (PhS) measure of the Child Health Questionnaire. The type of information captured by the PhS includes limitations in physical activity, limitations in the kind or amount of schoolwork or social activities the child engaged in, and presence of pain or discomfort.Results. One hundred thirty-one children were enrolled, a median center recruitment rate of 77%. The mean age of the participants was 9.6 years, and approximately half of the participants had completed less than the fourth grade at the time of enrollment. Sixty-two percent of the children were on prophylaxis at enrollment, and 9% had previously been on prophylaxis but were currently on on-demand therapy. Two groups were defined: ever treated with prophylaxis and never treated with prophylaxis. For those ever treated, treatment duration ranged from 2.7 months to 7.7 years, with one half of the children treated with prophylaxis for >40% of their lifetimes; 29% had always been on on-demand therapy. Children in both treatment groups were similar with respect to age, clotting factor level, parents' education, and IQ. The median number of bleeding episodes experienced in the year before enrollment for the cohort as a whole was 12. The median number of bleeding episodes in children on prophylaxis at enrollment was significantly lower than in children on on-demand therapy (6 vs 25.5).The mean achievement scores were within the average range of academic performance: reading, 100.4; mathematics, 101.6; language, 108.1; writing, 95.4; and total achievement, 102.5. When children were categorized as above or below the study group median by number of bleeding episodes, those who had a low number of bleeding e...

Long-term survival and improved neuropsychological function have occurred in selected children with Hurler syndrome (MPS I H) after successful engraftment with genotypically matched sibling bons marrow transplantation (BMT). However, because few children have HLA-identical siblings, the feasibility of unrelated donor (URD) BMT as a vehicle for adoptive enzyme therapy was evaluated in this retrospective study. Forty consecutive children (median, 1.7 years; range, 0.9 to 3.2 years) with MPS I H received high-dose chemotherapy with or without radiation followed by BMT between January 27, 1989 and May 13, 1994. Twenty-five of the 40 patients initially engrafted. An estimated 49% of patients are alive at 2 years, 63% alloengrafted and 37% autoengrafted. The probability of grade II to IV acute graft-versus-host disease (GVHD) was 30%, and the probability of extensive chronic GVHD was 18%. Eleven patients received a second URD BMT because of graft rejection or failure. Of the 20 survivors, 13 children have complete donor engraftment, two children have mixed chimeric grafts, and five children have autologous marrow recovery. The BM cell dose was correlated with both donor engraftment and survival. Thirteen of 27 evaluable patients were engrafted at 1 year following URD BMT. Neither T-lymphocyte depletion (TLD) of the bone marrow nor irradiation appeared to influence the likelihood of engraftment. Ten of 16 patients alive at 1 year who received a BM cell dose greater than or equal to 3.5 x 10(8) cells/kg engrafted, and 62% are estimated to be alive at 3 years. In contrast, only 3 of 11 patients receiving less than 3.5 x 10(8) cells/kg engrafted, and 24% are estimated to be alive at 3 years (P = .05). The mental developmental index (MDI) was assessed before BMT. Both baseline and post-BMT neuropsychological data were available for 11 engrafted survivors. Eight children with a baseline MDI greater than 70 have undergone URD BMT (median age, 1.5 years; range, 1.0 to 2.4 years). Of these, two children have had BMT too recently for developmental follow-up. Of the remaining six, none has shown any decline in age equivalent scores. Four children are acquiring skills at a pace equal to or slightly below their same age peers; two children have shown a plateau in learning or extreme slowing in their learning process. For children with a baseline MDI less than 70 (median age, 2.5 years; range, 0.9 to 2.9 years), post-BMT follow-up indicated that two children have shown deterioration in their developmental skills. The remaining three children are maintaining their skills and are adding to them at a highly variable rate. We conclude that MPS I H patients with a baseline MDI greater than 70 who are engrafted survivors following URD BMT can achieve a favorable long-term outcome and improved cognitive function. Future protocols must address the high risk of graft rejection or failure and the impact of GVHD in this patient population.

No abstract

Tested the influence of ability, time, quality of instruction, motivation, and academic coursework on high school students' achievement, also controlling for relevant background variables. Structural equation models were analyzed with longitudinal data from a national sample. Intellectual ability and academic coursework had powerful direct effects on achievement, and homework had a smaller direct effect. The indirect effects of quality of instruction and motivation were stronger than their direct effects; quality affected motivation, which affected coursework. Supplemental analyses were very consistent with the initial findings. Results support these variables as influences on school learning, a finding which also supports the theories from which the variables were derived. School learning theory and research are relevant for school psychologists who seek interventions for children with learning problems.Public and professional concern about the quality of American education highlights the need for a better understanding of the important influences on school learning.

Reported baseline findings from the neurological assessment component of the Hemophilia Growth and Development Study (HGDS). HIV-positive (HIV+; n = 207) and HIV-negative (HIV-; n = 126) young males with hemophilia ages 6 to 18 years, were enrolled in a prospective study of their growth and development. At baseline, HIV+ and HIV- subjects were not significantly different in test performance. The number of subjects exhibiting below-average performance in three or more areas assessed was about 25% overall. For both groups, mean test scores were within the average range. Academic and adaptive skills were lower than expected based on mean IQ scores, and more behavioral/emotional problems than expected were reported by parents. Absolute CD4 cell counts per mm3 were not related to neuropsychological performance at baseline. Results suggest that the subjects with HIV were relatively free of HIV-related neuropsychological impairment at baseline and that observed differences from a general population reflect effects of hemophilia as a chronic illness.