Pain In Infants and Young Children with Sickle Cell Disease-a Prospective Longitudinal Analysis

Abstract 841

Pain is the hallmark symptom of vaso-occlusion in sickle cell disease (SCD), but has not been well studied, particularly in children. Previous studies of pain in very young children with SCD have largely been limited to episodes sufficiently severe as to require acute care visits or hospitalizations. Our previous studies in school-aged children and adolescents (Dampier CD et al. J Pediatr Hematol Oncol 2004), as well as those in adults (Smith W et al Ann Inter Med 2009) suggest that vaso-occlusive pain is frequently managed at home outside of acute care medical settings. We sought to obtain similar data about the home pain experience of infants and young children with SCD as reported by parents or guardians, and to explore the relationship between the pain experience and hematological biomarkers. Enrollment and data collection was conducted from Jan 1999-Mar 2008 at the Marian Anderson Sickle Cell Center as part of the Comprehensive Sickle Cell Centers program. Families with SCD infants identified by newborn screening were first approached about the study after completion of confirmatory diagnosis and initial SCD-related education, usually between 4 to 6 months of age. After informed consent, parents/guardians were trained in pain assessment and daily reporting. When sickle cell related pain events occurred, parents/guardians reported pain occurrence, location, associated symptoms and the treatment that they provided. Daily paper diaries were generally used in the first year of life to familiarize families with pain assessment and reporting. Subsequently a novel daily pager system was used to provide a method allowed daily reporting, but with reduced participant burden. A monthly telephone system in conjunction with a daily calendar was used for those families unable to effectively comply with providing daily reports. All pain reports were adjudicated by consensus of study staff and PI/Co-PI. Children were removed from the study for any period of chronic transfusion for clinical events (splenic sequestration, recurrent acute chest syndrome, surgery). Over the study period, 103 children (58% male) were enrolled beginning at a median age of 7.3 months (range 1.5, 65.2 months). This represented about 50% of SCD children referred to the Center by newborn screening during these time periods; the most common reasons for refusal were inability to complete daily reporting and geographic distance from the Center. An SS genotype was present in 50 children (48.5%), SC in 32 (31.1%), SB0thalassemia in 6 (5.8%), SB+thalassemia in 15 (14.6%). Children were actively followed for a median of 3.8 years (range 0.3–7.6 years). The total number of days children were assessed for pain was 141,197 days with an additional 28,079 days of missing data (16%). The total number of days that children had reported pain was 2,288 days (1.6%), which represented 768 distinct episodes of pain. Over 80% of children reported to have pain in the 0–12 month age interval had pain locations (hands/feet) and characteristics (swelling or tenderness) consistent with dactylitis, which became progressively less prevalent in older age intervals. Significantly more SS/SB0 patients (58%) had >2 days of average dactylitis pain during 0–12 months or 12–24 months (53%) intervals compared to SC/SB+ patients (0%) (p=0.04). The timing of the first reported dactylitis event (<2 years or ≥2 years) significantly predicted the frequency of SCD pain events per person year, with earlier onset associated with more frequent pain events during the study period (p=0.02), for both the SS/SB0 and SC/SB+ (P=0.03) groups. Our study demonstrates the feasibility of initial recruitment and subsequent daily reporting of clinical events by families of infants and young children with SCD over many years, particularly when careful consideration is given to enhance family support and minimizing respondent burden. The onset of an initial dactylitis episode prior 2 years of age, even if treated at home, was associated with more frequent pain throughout childhood, irrespective of hemoglobinopathy type. Such children may be appropriate for interventions, such as oral hydroxyurea, that reduce excessive pain frequency. Supported by NIH HL-051495 and HL-083705.