Poster Presentation - SOMANZ ASM Society of Obstetric Medicine of Australia and New Zealand ASM 2023

Clinical Outcomes of Current Standard-of-Care in Pregnant Participants and Their Offspring at High Risk of Early-Onset Severe Hemolytic Disease of the Fetus and Newborn: Results from the Prospective Observational CLARITY Study (#57)

Dick Oepkes 1 , Kenneth J Moise Jnr 2 3 , Enrico Lopriore 4 , Eleanor Tiblad 5 6 , EJT (Joanne) Vertweij 1 , Rory Windrim 7 , Pranav Pandya 8 , Robert M Silver 9 , Stephen P Emery 10 , John Smoleniec 11 , Olga Ocon-Hernandez 12 , Rachel K Morris 13 , Diane D Harrison 14 , Valerie Smith 14 , Lisa B Schwartz 14 , May Lee Tjoa 14 , Leona E Ling 14 , Shumyla Saeed-Khawaja 14 , Yosuke Komatsu 14
  1. Department of Obstetrics, Department of Fetal Therapy, Leiden University Medical Centre, Leiden, The Netherlands
  2. Dell Medical School , University of Texas, Austin, Texas, United States
  3. Comprehensive Fetal Care Centre, Dell Children's Medical Centre, Austin, Texas, United States
  4. Department of Pediatrics, University of Leiden Medical Centre, Leiden, The Netherlands
  5. Centre for Fetal Medicine, Karolinska University Hospital, Stockholm, Sweden
  6. Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
  7. Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, Canada
  8. Fetal Medicine Unit, University College Hospital, Elizabeth Garrett Anderson Wing, London, United Kingdom
  9. Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, Utah, United States
  10. Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
  11. Feto-Maternal Unit, Liverpool Hospital, Liverpool, NSW, Australia
  12. Fetal Medicine Unit, San Cecilio University Hospital, Granada, Spain
  13. Fetal Medicine Centre, Birmingham Women's and Children's Foundation Trust, Birmingham, United Kingdom
  14. Spring House, Johnson & Johnson Pharmaceutical Companies, Pennsylvania, United States

Objective: Pregnancies at risk of early-onset severe hemolytic disease of the fetus and newborn (EOS-HDFN) are at high risk of poor outcomes. Standard-of-care (SOC) for pregnancies at risk of EOS-HDFN includes non-invasive monitoring for fetal anemia and intrauterine blood transfusions (IUTs) if fetal anemia manifests. Intravenous immunoglobulin (IVIG) or plasmapheresis may be administered to delay onset of fetal anemia and the need for IUT. The CLARITY trial aims to characterize the current SOC, clinical course, and outcomes at global HDFN referral centers for pregnant individuals and their offspring at high risk for EOS-HDFN.

 

Methods: CLARITY (NCT03755128), a prospective, global, multicenter, observational study, enrolled 15 alloimmunized pregnant participants with singleton pregnancies at high risk for EOS-HDFN based on a prior obstetric history of fetal loss, fetal hydrops, or severe fetal anemia at ≤24 weeks gestational age (GA) and a titer in the current pregnancy of >32 anti-D or >4 anti-Kell with confirmation of an antigen. The primary outcome is the proportion of participants with a live birth at ≥32 weeks GA without an IUT. Other perinatal and neonatal outcome variables are evaluated up to Day 28 postpartum of the last maternal participant.

 

Results: Primary outcome was achieved by 2/15 (13%) pregnant participants enrolled. 14/15 (93%) pregnancies resulted in a live birth, with a median GA at delivery of 36 2/7 weeks (31 4/7 to 38 0/7). Overall, 13/15 (87%) participants required IUTs, with a median of 4 (1-11) IUTs. The median GA at first IUT was 24 0/7 weeks (13 0/7 to 28 2/7). There was 1 (7%) case of hydrops fetalis. One pregnancy resulted in fetal demise which occurred at 16 5/7 weeks. Postnatal simple transfusions were required by 8/14 (57%) neonates/infants and exchange transfusions were required by 3/14 (21%). 4/13 (31%) maternal participants treated with IUT experienced complications. 7/15 (47%) maternal participants received IVIG. The 2 pregnant participants achieving primary outcome received IVIG. 3/7 (43%) participants who received IVIG experienced IVIG-related complications.

 

Conclusion: This prospective, observational study demonstrates that pregnancies at high risk for EOS-HDFN managed by SOC continue to experience significant unmet needs. Almost all required multiple IUTs, often starting <24 weeks GA, with a high complication rate even if IVIG was administered. These results highlight the medical need for an effective, non-invasive intervention for the treatment and management of pregnant individuals and their offspring at high risk for EOS-HDFN.