Clinical and Treatment Characteristics of Infants and Toddlers Less Than Two Years of Age with Hemophilia: A Report from the Community Counts Registry

Abstract

Introduction: Congenital hemophilia is an X-linked bleeding disorder often diagnosed in infants and toddlers (ITs) <2 years of age. Intracranial hemorrhage (ICH) in ITs with hemophilia remains a major complication, with a 7% occurrence, leading to disability and in some cases death. ICH in ITs may be preventable through delivery practices which avoid head trauma, especially when there is a family history (FH) of a bleeding disorder, and by early initiation of prophylaxis. The objective of this study was to examine the role of FH on mode of delivery, delivery practices, and initiation of prophylaxis, all within the context of the new treatment product emicizumab, which is approved for prophylaxis in individuals with hemophilia A (HA) of any age. We hypothesized that a FH of hemophilia would be associated with lower proportion of vaginal deliveries and instrumentation at birth and earlier age of prophylaxis initiation. Methods: We included ITs who were <2 years of age and enrolled in Community Counts, a US based Registry for Bleeding Disorders Surveillance that collects data from individuals who receive care at federally funded hemophilia treatment centers. The analysis was limited to initial surveillance visits through 2021 for ITs born ≥2011 and diagnosed with congenital HA or hemophilia B (HB), with a clotting factor activity level of <50%. Analyzed data included socio-demographics, FH of hemophilia (defined as parent report of one or more blood relative), mode of delivery (including the presence or absence of instrumentation), diagnosis type, age at diagnosis, ICH, treatment product usage, head trauma, and age at prophylaxis initiation. Summary statistics were used to characterize demographic and clinical information by FH. Differences between FH, demographic and clinical information, as well as differences between birth cohorts (2011-2015, 2015-2018, and 2019-2021) and treatment product usage were assessed for statistical significance using chi-square or parametric or non-parametric tests of differences between means as appropriate. Results: Of the 883 ITs in the analysis, most were male (98%), White (73%), non-Hispanic (78%), with HA (78%), severe disease (62%), and a known FH (70%). ITs with a FH had a lower proportion of vaginal deliveries than those with no FH (67% vs. 80%, p = 0.0006) and less instrumentation with vaginal delivery (4% vs. 9%; p = 0.02). ITs with a FH were also diagnosed earlier than those without a FH (p = <0.0001); however, age of prophylaxis initiation was not significantly different between ITs with vs without a FH (10.0 mo ± 6.2 versus 11.2 mo ± 6.0; p = 0.17) [Table 1]. Sixty-eight (8%) ITs had one or more ICH during the first two years of life. ITs with a FH were slightly less likely to have an ICH than those with no FH, but the difference was not statistically significant (7% vs 11%, p=0.08). Among all ITs with an ICH, 8 (12%) were on continuous prophylaxis at the time of ICH and 24 (35%) experienced ICH within the first month of life. Of the 24 with ICH in the first month of life, 17 (71%) had vaginal delivery and 8 (33%) reported head trauma. Regarding prophylaxis, 205 (30%) ITs with HA were on continuous prophylaxis within the first two years of life, 91% with severe HA. Thirty-five (18%) with HB were on continuous prophylaxis, 88% with severe HB. Prophylaxis with extended half-life (EHL) clotting factor and emicizumab increased over the study period for ITs with HB and HA respectively. Additionally, ITs with HA born after 2018 started prophylaxis sooner than those born in earlier years (Table 2). Conclusions: The ICH rate of 8% in ITs in this study is substantial and similar to prior reports. This study showed that a known FH of hemophilia was associated with earlier age of diagnosis and decreased rate of vaginal delivery. Nonetheless, the proportion of ICH was only slightly lower among ITs with a FH than those with no FH, and the difference did not reach statistical significance. EHL clotting factor and emicizumab use for prophylaxis increased across the birth cohorts reflecting the addition of new treatment options. The age of prophylaxis initiation decreased in ITs with HA, perhaps reflecting easier mode of administration and national guidelines supporting early initiation to prevent ICH. In ITs with hemophilia there remains opportunity to further reduce ICH by identifying at risk fetuses, optimizing delivery plans to minimize head trauma, and initiating prophylaxis even within the first month of life. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal