Randomized Controlled Trials
SPIN Pilot RCT – Lead Site
Single-dose Prophylactic Indomethacin in Extremely Preterm Infants – A Multicenter Pilot Randomized Blinded Placebo-Controlled Trial
Each year in Canada, approximately 900 infants are born extremely preterm at less than 26 weeks gestation (GA. Nearly four out of 10 of these infants will not survive or develop a devastating neurological complication called severe intraventricular hemorrhage (sIVH). Existing evidence shows that a 3-dose regimen of intravenous indomethacin (0.1mg/kg/dose every 24h for 3 doses), given shortly after birth, significantly reduces the incidence of death and severe brain injury. However, use of this conventional regimen has declined due to concerns about potential gastrointestinal side effects.
Recent pharmacokinetic studies show that indomethacin clearance is significantly reduced in the first week of life of infants born ≤26 weeks GA due to their developmental immaturity. As a result, a single 0.1 mg/kg dose maintains therapeutic levels for at least 72h – the most critical period for sIVH onset in these smallest infants.
This pilot trial will assess the feasibility of conducting a definitive trial to explore the following research question: In extremely preterm infants born <26 weeks GA, does a single prophylactic dose of intravenous indomethacin (0.1 mg/kg)), given within 12 hours of birth, reduce morbidity and mortality compared to a saline placebo?
ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT06572917
This study is being funded by CIHR.
For more information about the study, contact the study coordinator at michelle.avina@cw.bc.ca.
Prospective Clinical Studies
The impact of low dose dexamethasone (DART) treatment in neonates on echocardiographic markers of cardiac function and pulmonary hypertension (Dr. Judith Leyens)
Approximately 10% of all babies are born prematurely and one of the most common complications associated with prematurity is chronic lung disease (CLD) or bronchopulmonary dysplasia (BPD). Complex cardiovascular interplay can further predispose these vulnerable infants to develop pulmonary hypertension (PH), a serious and potentially life-threatening condition. While many different approaches exist to prevent and treat evolving or established BPD, postnatal corticosteroids are one of the most commonly used. However, previous studies have been limited by small sample sizes and short-term follow-up periods, typically 7-14 days post-treatment. Our study aims to address these gaps by prospectively evaluating the echocardiographic and clinical impact of low-dose dexamethasone treatment (DART) in a larger cohort of extremely preterm infants (<28 weeks gestational age), with assessments conducted up to 72 hours before and after DART, as well as at 32 weeks gestational age, to capture both immediate and longer-term outcomes.
For more information about the study, contact the research coordinator at michelle.avina@cw.bc.ca.
Agreement, Reliability, and Validity of Automated Versus Manual Simpson’s Biplane Ejection Fraction in Neonates: An Observational Cohort Study (Dr. Mohammed Ellebany)
Targeted Neonatal Echocardiography (TNE) is an important bedside tool that helps neonatologists assess and manage the cardiovascular status of critically ill newborns. Left ventricular ejection fraction (LVEF) is a key measure of heart function and plays an important role in clinical decision-making. This study evaluates the performance of fully automated artificial intelligence (AI)-generated LVEF measurements with the manual Simpson’s biplane method in neonates undergoing TNE.
For more information about the study, contact the research coordinator at: michelle.avina@cw.bc.ca.
Retrospective Studies
Prophylactic Indomethacin in MicropreemiEs: A Retrospective Cohort Study (PRIME) – Una Spasovski
Severe intraventricular hemorrhage (sIVH) remains a major contributor to morbidity and mortality among micropreemies. Clinical trials have shown that prophylactic indomethacin reduces the incidence of sIVH, an outcome deemed critical by families. However, its use remains inconsistent due to concerns about potential adverse effects. To address this gap, Una led a retrospective cohort study linking data from the Canadian Neonatal Network (CNN) and Canadian Neonatal Follow-Up Network (CNFUN). The study will evaluate whether prophylactic indomethacin improves survival at NICU discharge and reduces significant neurodevelopmental impairment at 18–24 months in infants born at less than 26 weeks’ gestation.
This project, Prophylactic Indomethacin in Micropreemies (PRIME), has been presented at several national and international conferences, including the CNN Annual Meeting (Feb 11, 2025), CANTRAIN's 2nd National Conference (Feb 25, 2025), Neonatal Follow-Up Program Research Day (April 4, 2025), UBC Department of Pediatrics Celebrate Research Day (April 11, 2025), Pediatric Academic Societies Meeting (April 28, 2025) and the Canadian National Perinatal Research Meeting (May 13, 2025).
Impact of Patent Ductus Arteriosus (PDA) on Chronic Pulmonary Hypertension in Micropreemies: Assessing Disease Severity and Phenotypes using a Novel Scoring System – Caia Fisher-Hulse
Patent ductus arteriosus (PDA) is a common physiological cardiovascular condition affecting many extremely preterm infants. In addition to the presence of a PDA, many conditions can develop attributed to the underdeveloped cardiopulmonary systems in micropreemies, including chronic pulmonary hypertension. The effect of prolonged PDA exposure on the development of cPH in micropreemies remains unclear. My research develops a novel scoring system to assess both the disease severity and phenotype of cPH likely to develop in micropreemies. The second part of the project involves testing this scoring system on clinical trial data from the SMART-PDA study, to investigate the impact of persistent PDA on the severity and phenotypes of chronic pulmonary hypertension. This project aims to advance the understanding of PDA-cPH interactions, support future trials, and provide neonatologists with a clinically meaningful tool to improve the assessment and management of the sickest extremely preterm infants.
This project was presented at the UBC Women+ and Children’s Health Sciences Research Day (April 2025).
SMART-PDA Lite: Examining the Validity of a Simplified SMART-PDA Treatment Algorithm – Caia Fisher-Hulse
When deciding whether to treat or conservatively manage patent ductus arteriosus (PDA) in extremely preterm infants, neonatologists utilize targeted neonatal echocardiography to support clinical findings. This combination of echocardiographic measurements and clinical criteria has been optimized in the SMART-PDA clinical trial, to assess whether PDA should be treated in extremely preterm infants. This study, a SMART-PDA sub-study, explores whether a simplified selective early medical treatment criteria (SMART-PDA lite) can lead to the same treatment decisions made by the original SMART criteria. Simplified echocardiographic and clinical treatment parameters may facilitate streamlined decision making, improve feasibility in clinical practice, and support broader implementation of the SMART strategy.
This project was presented at the 2025 NeoHeart Conference in San Diego (July 29-August 1, 2025), BC Women’s Hospital NICU Research & Quality Improvement Rounds (September 5, 2025), the Paediatric Inpatient Research Network Meeting (November 14), and the BC Division of Neonatology Clinical Associates Teaching Symposium (November 27, 2025).
Reliability of two-dimensional mode versus M-mode echocardiography for measurement of left atrium/aortic diameter ratio and fractional shortening in extreme preterm infants – Dr. Uthaya K. Kanagaraj
In extremely preterm infants, targeted neonatal echocardiography (TNE) is increasingly used to assess the hemodynamic status of newborns with patent ductus arteriosus (PDA). Two TNE measurements used to evaluate hemodynamically significant PDA are the left atrium to aortic root ratio (LA:Ao), which reflects left heart volume overload, and fractional shortening (FS), which assesses left ventricular function. These parameters are most commonly measured using M-mode imaging in current TNE protocols. However, this practice differs from the American Society of Echocardiography pediatric guidelines, which recommend using 2D-imaging for FS and offer no specific guidance for LA:AO measurement. This study aims to evaluate the interrater reliability of M-mode versus 2D-mode measurements of LA:Ao and FS in infants born before 29 weeks gestation.
This study was presented as an oral presentation at the E2i Research Day (Feb 25, 2025), NICU Research and Quality Improvement Rounds (March 14, 2025) and in the recently concluded Pediatric Academic Societies Meeting in Hawaii as a poster presentation.
NeoSTAR – Caia Fisher-Hulse
Neonatal transport is a critical and specialized service ensuring the safe and timely transport of newborns to hospitals equipped to meet their needs. Delays in the transport process can negatively affect outcomes, making efficient team dispatch—known as mobilization time—a key quality indicator. To address disparities in transport team availabilities, NeoSTAR was implemented, a hospital-based neonatal transport team for the transport of low to moderate acuity patients in the Lower Mainland. This project, a quality analysis initiative, will compare mobilization times before and after NeoSTAR’s implementation to determine whether the program improves mobilization times. Findings will inform future program development with the goal of increasing the acuity of transport cases.
Evidence Synthesis
Early erythropoiesis-simulating agents in preterm or low birth weight infants: update of a Cochrane Systematic Review – Dr. Kia Anarna
We have updated the evidence through a systematic review of randomized controlled trials on the efficacy of early erythropoiesis-stimulating agents such as erythropoietin and darbepoetin among preterm and low birth weight infants on outcomes such as mortality, neurodevelopmental impairment, retinopathy of prematurity, necrotizing enterocolitis, severe intraventricular hemorrhage, and number of transfusions among others. Certainty of evidence was assessed using GRADE and subgroup analysis of high-quality trials was done. Erythropoietin was found to have consistent hematopoietic benefits among preterm and low birth weight infants with a relatively good safety profile.
This project has been presented as an oral presentation at the Neonatal Follow-up Research Day (April 4, 2025), UBC Department of Pediatrics Celebrate Research Day (2nd place best fellow research, April 11, 2025), Pediatric Academic Societies Meeting in Honolulu (April 27, 2025), and the District VIII Conference in Boise Idaho (June 6, 2025).
Can Agentic AI Replicate a Cochrane Neonatal Systematic Review? An Evaluation Using Loon Lens – Caia Fisher-Hulse
The Cochrane methodology for conducting systematic reviews is the gold standard for producing comprehensive evidence synthesis leading to changes in evidence-based medicine and clinical guidelines. However, the traditional review process requires substantial time and resources. Using Loon Lens, a large language model-driven agentic AI platform, the systematic review process can be fully automated from building a search strategy to data extraction. This project sets out to comprehensively evaluate the ability of the Loon Lens agentic AI platform to autonomously replicate the high impact Cochrane Neonatal systematic review: “Early treatment versus expectant management of hemodynamically significant patent ductus arteriosus for preterm infants”.
This project was presented as an oral presentation at the Professor Robert Hill Memorial Lectureship (November 28, 2025). It will be presented as an oral presentation at the upcoming Pediatric Academic Societies Meeting in Boston this April, 2026.
Recently Completed Projects
SMART-PDA Pilot RCT- awaiting publication
Trial registration: https://clinicaltrials.gov/study/NCT05011149
Protocol: https://bmjopen.bmj.com/content/14/7/e087998
CANRxPDA - awaiting publication
Study registration: https://clinicaltrials.gov/study/NCT04347720
Protocol: https://bmjopen.bmj.com/content/11/5/e050682.long