Two-year outcomes following a randomised platelet transfusion trial in preterm infants.
OBJECTIVE: Assess mortality and neurodevelopmental outcomes at 2 years of corrected age in children who participated in the PlaNeT-2/MATISSE (Platelets for Neonatal Transfusion - 2/Management of Thrombocytopenia in Special Subgroup) study, which reported that a higher platelet transfusion threshold was associated with significantly increased mortality or major bleeding compared to a lower one. DESIGN: Randomised clinical trial, enrolling from June 2011 to August 2017. Follow-up was complete by January 2020. Caregivers were not blinded; however, outcome assessors were blinded to treatment group. SETTING: 43 level II/III/IV neonatal intensive care units (NICUs) across UK, Netherlands and Ireland. PATIENTS: 660 infants born at less than 34 weeks' gestation with platelet counts less than 50×109/L. INTERVENTIONS: Infants were randomised to undergo a platelet transfusion at platelet count thresholds of 50×109/L (higher threshold group) or 25×109/L (lower threshold group). MAIN OUTCOMES MEASURES: Our prespecified long-term follow-up outcome was a composite of death or neurodevelopmental impairment (developmental delay, cerebral palsy, seizure disorder, profound hearing or vision loss) at 2 years of corrected age. RESULTS: Follow-up data were available for 601 of 653 (92%) eligible participants. Of the 296 infants assigned to the higher threshold group, 147 (50%) died or survived with neurodevelopmental impairment, as compared with 120 (39%) of 305 infants assigned to the lower threshold group (OR 1.54, 95% CI 1.09 to 2.17, p=0.017). CONCLUSIONS: Infants randomised to a higher platelet transfusion threshold of 50×109/L compared with 25×109/L had a higher rate of death or significant neurodevelopmental impairment at a corrected age of 2 years. This further supports evidence of harm caused by high prophylactic platelet transfusion thresholds in preterm infants. TRIAL REGISTRATION NUMBER: ISRCTN87736839.
Peer reviewed: True
Acknowledgements: We thank all the hospital staff and research teams who helped conduct this trial (for a complete list, see the online supplemental appendix), all the families who agreed to participate; Dr Shobha Cherian, consultant neonatologist and principal investigator at University Hospital of Wales, Cardiff, and Anna Hendrickson, research nurse at St. Mary’s Hospital, Manchester, both of whom died in 2015 and 2016, respectively, for their valued contributions to and enthusiasm in the success of the trial; the National Health Service Blood and Transplant Clinical Trials Unit team, including Anna Sidders and Heather Smethurst (trial coordinators), Nikki Dallas (database manager), Louise Choo, Brennan Kahan, Helen Thomas, Laura Pankhurst and Agne Zarankaite (trial statisticians), and Colin Morley, Sandy Calvert and Anthony Emmerson (trial steering committee) for their support; and Adrian Newland, Henry Halliday, Paul White, Gavin Murphy, Michael Greaves, Keith Wheatley and Marc Turner (the data and safety monitoring committee).
Funder: National Institute for Health Research; FundRef: http://dx.doi.org/10.13039/501100000272
Funder: Addenbrooke's Charitable Trust, Cambridge University Hospitals; FundRef: http://dx.doi.org/10.13039/501100002927
Stichting Sanquin Bloedvoorziening (PPOC-12-012027)
NHS Blood and Transplant (BS06/1)
Neonatal Breath of Life Fund (9145)