Derek P de Winter, Kenneth J Moise, Leona E Ling, Dick Oepkes, Eleonor Tiblad, E J T Joanne Verweij, John Smoleniec, Ulrich J Sachs, Gregor Bein, Mark D Kilby, Russell S Miller, Roland Devlieger, Anne Debeer, Jocelyn H Leu, Robert M Nelson, Valerie Smith, Lisa B Schwartz, May Lee Tjoa, Yosuke Komatsu, Shumyla Saeed-Khawaja, Enrico Lopriore, UNITY Study Group
Maternal nipocalimab in pregnancies at high risk of EOS-HDFN may reduce adverse neonatal outcomes correlating with low cord-blood alloantibody titres, without affecting growth through 6 months, neurodevelopment or HRQoL through 24 months of life.
OBJECTIVES: To describe haemolytic disease outcomes, growth, neurodevelopment and health-related quality of life (HRQoL) through 24 months of life in infants exposed to nipocalimab in pregnancies at high risk of early-onset severe haemolytic disease of the fetus and newborn (EOS-HDFN).
DESIGN: A multicentre, open-label, single-arm trial.
SETTING: Centres with expertise in HDFN management.
PATIENTS: Pregnant individuals with previous EOS-HDFN and maternal anti-D titres ≥32 or anti-K titres ≥4.
INTERVENTIONS: Weekly nipocalimab (30 and/or 45 mg/kg) from 14 to 35 gestational weeks.
MAIN OUTCOME MEASURES: Infants' cord-blood alloantibody titres at birth, HDFN management, growth through 6 months, neurodevelopment (caregiver-reported Ages and Stages Questionnaire, third edition (ASQ-3)) and HRQoL assessments through 24 months of life.
RESULTS: Of 13 pregnancies, 12 resulted in live births; one fetal loss occurred due to intrauterine transfusion (IUT) complications. A single simple transfusion was administered in one of seven infants delivered after a maternal nipocalimab course without IUTs, where cord blood alloantibody titres were <8. Multiple transfusions (one to seven simple transfusions/infant; one exchange transfusion) were administered to five infants delivered after early nipocalimab discontinuation and IUTs, with cord-blood alloantibody titres ranging from 512 to 32 768. No unusual growth patterns were observed through 6 months. No neurodevelopmental delays were identified through 24 months of life, with mean ASQ-3 domain scores within normal ranges. HRQoL outcomes were positive across physical, emotional, social and cognitive functioning.
CONCLUSIONS: Maternal nipocalimab in pregnancies at high risk of EOS-HDFN may reduce adverse neonatal outcomes correlating with low cord-blood alloantibody titres, without affecting growth through 6 months, neurodevelopment or HRQoL through 24 months of life.
TRIAL REGISTRATION NUMBER: NCT03842189.