Objectives To develop a flexible droplet digital PCR (ddPCR) workflow to perform non‐invasive prenatal diagnosis via relative mutation dosage (RMD) for maternal pathogenic variants with a range of inheritance patterns, and to compare the accuracy of multiple analytical approaches. Methods Cell free DNA (cfDNA) was tested from 124 archived maternal plasma samples: 88 cases for sickle cell disease and 36 for rare Mendelian conditions. Three analytical methods were compared: sequential probability ratio testing (SPRT), Bayesian and z‐score analyses. Results The SPRT, Bayesian and z‐score analyses performed similarly well with correct prediction rates of 96%, 97% and 98%, respectively. However, there were high rates of inconclusive results for each cohort, particularly for z‐score analysis which was 31% overall. Two samples were incorrectly classified by all three analytical methods; a false negative result predicted for a fetus affected with sickle cell disease and a false positive result predicting the presence of an X‐linked IDS variant in an unaffected fetus. Conclusions ddPCR can be applied to RMD for diverse conditions and inheritance patterns, but all methods carry a small risk of erroneous results. Further evaluation is required both to reduce the rate of inconclusive results and explore discordant results in more detail.

Over 95% of children with sickle cell disease (SCD) survive into adulthood in the United States. However, early mortality remains a problem, especially in persons between the ages of 18 and 35. One possible explanation for the increased mortality rate in young adults is difficulties in engaging in care during the transition from a heavily contiguous pediatric healthcare model to a more self‐reliant adult healthcare model. The goal of this study was to identify potential facilitators and barriers to a successful transfer in care from the pediatric to adult SCD program before the formation of a formal transition program. This is a retrospective cohort study of transition outcomes for 472 individuals with SCD (all genotypes) treated at the University of Alabama at Birmingham (UAB) sickle cell clinic (aged 18–24). The primary outcome was whether the patient continued care in (any) adult SCD program (defined as being seen at least once in an adult hematology/SCD clinic). One hundred eighty‐eight (45%) transition age patients successfully transferred to adult care. Facilitators to successful transfer in care included being treated at the same hospital for both pediatric and adult programs, having the genotype HbSS, and/or receiving an SCD‐modifying therapy at the time of transition (hydroxyurea and/or red cell transfusion therapy). Of primary interest, many of the patients who failed to transition to an adult clinic were lost to follow‐up prior to 15 years of age. Importantly, these patients who had previously been labeled as “transition failures,” were lost to follow‐up long before the transition age. Early engagement is needed for this population.

IMPACT: To identify potential facilitators and barriers to a successful transition in care. OBJECTIVES/GOALS: Improvements in care for children with sickle cell disease (SCD) have increased survival into adulthood. However, mortality rates are increasing in young adults. One of the challenges is providing appropriate care during transition from pediatric to adult care. The goal is to identify facilitators and barriers to a successful transition in care. METHODS/STUDY POPULATION: The UAB SCD Center serves a large area of Alabama. The pediatric program is in Birmingham and has outreach clinics in three other cities. The adult program only has one clinic located in Birmingham. With IRB approval, we performed a retrospective chart review of individuals with SCD (all genotypes) aged 18-24 (as of 1/31/2019) who were seen at least twice prior to age 18 (in pediatrics) and have confirmed SCD. Charts were reviewed for demographics, genotype, last known insurance, SCD therapy, clinic location, and transition status. Analyses were undertaken to determine predictors of successful transition (defined as coming to an appointment with an adult hematologist) and unsuccessful transition (defined as lost to follow-up (LTFU) without transfer of care). RESULTS/ANTICIPATED RESULTS: There were 544 individuals meeting inclusion criteria. Of this group, 234 were LTFU, 189 transitioned, 36 moved, and 15 died. Seventy patients are still under pediatric care and were excluded. Sixty-eight percent of patients that transitioned had their last pediatric visit in Birmingham, compared to only 32% of those that transitioned from outreach sites (p<.01). Patients were more likely to successfully transition if they had sickle cell anemia (HbSS or HbSß0) (p<.01) and if they were receiving hydroxyurea or chronic transfusion therapy (p<.01). DISCUSSION/SIGNIFICANCE OF FINDINGS: Geography, genotype, and SCD therapy are potential drivers for transition. Genotype in pediatrics likely confers disease severity, suggesting patients with worse SCD may be more likely to successfully transition. Novel strategies are needed to improve transition of care for patients outside of Birmingham and those with less severe disease.