Defining the Impact of Hemophilia: The Academic Achievement in Children With Hemophilia Study Amy D. Shapiro, MD*; Sharyne M. Donfield, PhD‡; Henry S. Lynn, PhD‡; Valerie A. Cool, PhD§; James A. Stehbens, PhD§; Scottie L. Hunsberger‡; Sharon Tonetta, PhD; Edward D. Gomperts, MD; and the Academic Achievement in Children with Hemophilia Study Group ABSTRACT. Objectives. We characterized a popula- tion-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, mea- sured 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 investi- gation 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 occur- rence 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 en- rolled, a median center recruitment rate of 77%. The mean age of the participants was 9.6 years, and approxi- mately 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 enroll- ment, 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 dura- tion 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 expe- rienced 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 signifi- cantly 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; mathe- matics, 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 episodes (<11) had better total achievement (104.4 vs 100.6) and mathematics (103.6 vs 99.6) than chil- dren in the higher bleeding episode category (>12) after adjusting for child’s IQ and parents’ education. Treat- ment with prophylaxis per se was not associated with better test scores, but children who had been treated on a regimen of long-term prophylaxis (>40% of lifetime) and reported <11 bleeding episodes in the year before enroll- ment had significantly higher scores in total achievement (104.9 vs 100.6), mathematics (105.2 vs 99.6), and reading (104.0 vs 98.6) than all other children reporting >12 bleeding episodes in the same time period. Increased school absenteeism and hemophilia-related limitations in physical functioning among children with greater fre- quency of bleeding episodes were proposed as the mech- anisms for lower scores. The number of bleeding epi- sodes was positively correlated with school absenteeism (Spearman correlation  0.23), and children with more school absences had lower scores in mathematics, read- ing, and total achievement, even after adjusting for the child’s IQ and parents’ education. Children with fewer bleeding episodes also had better PhS scores than chil- dren in the high bleeding episode category (48.4 vs 41.3). The mean PhS for children in the low bleeding episode group (48.4) was similar to that of the general US popu- lation (50), but the mean PhS for children in the higher bleeding episode group was almost a full standard devi- ation lower than the mean for the general US population. PhS scores were positively related to reading and total achievement scores after adjusting for IQ and parents’ education. Of interest and concern was a group of children who were reportedly being treated with prophylaxis during the year before enrollment (N  18) but whose bleeding events were not optimally suppressed. These children were 3 times as likely (33.3% vs 11.1%) to be receiving <2 infusions per week as children on prophylaxis who re- ported <11 bleeding episodes during the same period. A review of the sites of bleeding reported for the 18 chil- dren revealed that 12 (66.6%) experienced >25% of their bleeding episodes in the same joint. From the *Indiana Hemophilia and Thrombosis Center, Indianapolis, Indi- ana; ‡Rho, Inc, Chapel Hill, North Carolina; §University of Iowa Hospitals and Clinics, Iowa City, Iowa; Baxter Healthcare Corporation, Hyland Im- muno Division, Glendale, California. Received for publication Apr 17, 2001; accepted Aug 16, 2001. Reprint requests to (A.D.S.) Indiana Hemophilia and Thrombosis Center, 8402 Harcourt Rd, Suite 420, Indianapolis, Indiana 46260. E-mail: ashapiro@ihtc.org PEDIATRICS (ISSN 0031 4005). Copyright © 2001 by the American Acad- emy of Pediatrics. http://www.pediatrics.org/cgi/content/full/108/6/e105 PEDIATRICS Vol. 108 No. 6 December 2001 1 of 6 by guest on April 13, 2017 Downloaded from