WIP 17 - PRophylactic Indomethacin in MicropreemiEs (PRIME) – a retrospective cohort study

Publication Number: WIP 17.7536

Una Spasovski, University of British Columbia Faculty of Medicine, VANCOUVER, BC, Canada; Souvik Mitra, University of British Columbia Faculty of Medicine, Vancouver, BC, Canada; Lindsay Richter, University of British Columbia, Vancouver, BC, Canada; Marc Beltempo, McGill University Faculty of Medicine and Health Sciences, Montreal, PQ, Canada; Thuy Mai Luu, Centre Hospitalier Universitaire Sainte-Justine, Montreal, PQ, Canada; Joseph J. Ting, University of Alberta, Edmonton, AB, Canada; Jonathan Wong, University of British Columbia Faculty of Medicine, Vancouver, BC, Canada; Emily Kieran, Children's and Women's Health Centre of BC, Vancouver, BC, Canada; Jehier Afifi, Dalhousie University, Halifax, NS, Canada; Jessie VanDyk, BC Women's Hospital, Vancouver, BC, Canada; Steven Miller, University of British Columbia Faculty of Medicine, Vancouver, BC, Canada; Robert Platt, McGill University Faculty of Medicine and Health Sciences, Montreal, PQ, Canada; Jeffrey N.. Bone, BCCHR, Vancouver, BC, Canada; Fabiana Bacchini, Canadian Premature Babies Foundation, Etobicoke, ON, Canada; Tom Wiebe, BC Women's Hospital, Vancouver, BC, Canada

Background: Severe intraventricular hemorrhage (IVH) is an important contributor to morbidity and mortality in preterm infants, especially those born < 26 weeks’ GA. Existing evidence shows that prophylactic intravenous indomethacin results in a significant reduction in sIVH, an outcome deemed critical by families. However, the use of indomethacin prophylaxis is highly variable among clinicians due to perceived adverse effects.

Objective: To determine the effectiveness and safety of prophylactic indomethacin in reducing (1) mortality and morbidity at NICU discharge, and (2) significant neurodevelopmental impairment (NDI) at 18-24 months corrected age (CA) follow-up assessment in extremely preterm infants born < 26 weeks’ GA.

Design/Methods: We conducted a retrospective, multicenter cohort study utilizing real-world data collected from the Canadian Neonatal Network (CNN) and Canadian Neonatal Follow-up Network (CNFUN). We included preterm infants born < 26 weeks' GA between 2010 and 2021, admitted across CNN centers and eligible to be seen at participating CNFUN sites for follow-up assessment. We emulated a target trial to compare prophylactic intravenous indomethacin initiated within 24 hours of birth to no indomethacin treatment (IRB: H24-02225).
Approach & Outcomes:
For objective 1, we used data from the CNN to create a NICU cohort of 5000 infants; Primary outcome: survival at NICU discharge.
For objective 2, we linked this NICU cohort to the CNFUN database to create a follow up cohort who underwent developmental assessment at 18-24 months CA; Primary outcome: Significant NDI among survivors (“significant” defined as cerebral palsy classified as GMFCS 3,4 or 5, Bayley motor, cognitive or language scores < 70, hearing loss requiring aid or implant, and/or bilateral visual impairment).
Analysis (in progress): Multivariable analyses are being conducted to compare primary outcomes between groups using 3 models –propensity score matching, inverse probability weighted analysis and generalized estimating equations to account for potential confounders and clustering within each NICU.