This study longitudinally observes the intergenerational (mother-child) continuum in hemophilia A from pregnancy through early childhood. Because the study follows mother-child pairs, the study includes both a maternal cohort and a pediatric cohort. Each cohort has a primary goal: for the mother with a severe hemophilia genotype, the overarching primary goal is to understand the risks for pregnancy-associated bleeding and postpartum hemorrhage (PPH); for the child, the overarching primary goal is to understand the risks, timing, and circumstances of development of anti-FVIII antibodies. From a longitudinal perspective, risks for both bleeding in the mother and anti-FVIII antibody development in the child are expected to be influenced over time by genetic and environmental factors that begin early in (or before) pregnancy. Enrollment of blood relatives is offered to improve power to better understand inherited contributions to bleeding and inhibitor development in the mother-baby pairs.
Currently pregnant and prior to 37 weeks gestation
Known to have or at-risk of having a severe hemophilia A genotype
Pregnant with at least one fetus at-risk of inheriting severe hemophilia A
Ability to understand and willingness to provide informed consent
None
To accomplish the goal of following 50 mother-child pairs with a child affected by severe hemophilia A from pregnancy through at least the first 2 years of life, we expect to enroll approximately 120 pregnant mothers with a pregnancy at-risk of being affected by severe hemophilia A. Blood relatives of the child can also enroll.
Cohort
Prospective
Not listed
Primary Endpoint(s)/Outcome(s)
The study primary endpoints/outcomes for the maternal and pediatric cohorts are as follows: • Maternal: Rates of primary PPH, defined as * estimated or quantified blood loss \> 1,000 mL in the first 24 hours PP, or * unplanned transfusion of blood products related to blood loss in the first 24 hours PP. As a subset of primary PPH, severe primary PPH is defined as * estimated or quantified blood loss \> 1,500 mL or requirement of \> 2 units packed red blood cells within 24 hours PP, or * primary PPH with estimated or quantified blood loss \> 1,000 mL and evidence of maternal hemodynamic instability (tachycardia, hypotension) or end organ damage with no other etiology (oliguria, creatinine \> 0.8, etc.). • Pediatric: Rate of development of humoral immune response to FVIII and proportion that progress to clinical inhibitors, defined as * clinical FVIII inhibitor, or * detection of an antibody specific to FVIII.
Secondary Endpoint(s)/Outcome(s)
Prioritized Secondary Maternal and Pediatric Endpoints/Outcomes * Maternal: Rate of secondary PPH * Maternal: Development of other clinically significant other bleeding * Pediatric: Development of clinical FVIII inhibitor * Pediatric: Development of IgG1 antibody to FVIII * Pediatric: Development of high-affinity IgG3 or IgG4 antibody to FVIII Additional descriptions of study outcomes and hypotheses to be tested are detailed in the study protocol.
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University of Washington
Lead sponsor
National Heart, Lung, and Blood Institute (NHLBI)
Collaborator
RTI International
Collaborator
Emory University
Collaborator
