560 - Association of Trial Enrollment with 22–26-month Corrected Age Outcomes in Extremely Preterm Infants: A Retrospective Cohort Study

Publication Number: 560.3665

Rebecca A. Dorner, Sharp Mary Birch Hospital for Women & Newborns, San Diego, CA, United States; shampa saha, RTI international, Durham, NC, United States; Elizabeth Foglia, Childrens Hospital of Philadelphia, Philadelphia, PA, United States; Sara B.. DeMauro, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States; Abhik Das, RTI International, North Potomac, MD, United States; Matthew Rysavy, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, TX, United States; Jenny K.. Koo, Sharp Mary Birch, San Diego, CA, United States; Tarah Colaizy, University of Iowa Stead Family Children's Hospital, Iowa City, IA, United States; Robin K. Ohls, University of Utah, Salt Lake City, UT, United States; Haresh Kirpalani, Childrens Hospital of Philadelphia, Philadelphia, PA, United States; Kristi L. Watterberg, University of New Mexico School of Medicine, ALBUQUERQUE, NM, United States; Edward F. Bell, University of Iowa, Iowa City, IA, United States; Anup Katheria, Sharp Mary Birch Hospital for Women & Newborns, San Diego, CA, United States; NICHD Neonatal Research Network, National Institute of Child Health and Human Development, Bethesda, MD, United States

Background: Previous studies have examined short-term outcome differences among extremely preterm infant trial participants and those eligible but non-enrolled. Potential longer-term benefits of trial participation in this population have not been well-studied.

Objective: To determine if survival or survival without neurodevelopmental impairment (NDI) at 22-26 months’ corrected age is more common among extremely premature infants enrolled in comparative effectiveness randomized controlled trials (RCTs), compared to those eligible but not enrolled.

Design/Methods: Retrospective cohort study at 15 U.S. NICHD Neonatal Research Network (NRN) centers. Liveborn inborn infants born < 27 weeks’ gestation from 2014-2019 who were eligible for 1 or more of 3 RCTs (MILK, Hydrocortisone for BPD, and TOP trials), survived at least 12 hours, and had follow-up data at 22-26 months’ corrected age were included. Logistic regression models were developed to test the relationship between trial participation and death or survival without NDI. Models were adjusted for maternal and infant factors known to affect mortality and developmental outcomes.

Results: There were 1659 infants enrolled in at least one RCT and 1497 infants eligible but not enrolled. Follow-up rates were 94% for enrolled and 85% for eligible non-enrolled infants. 47.5% of screened infants were deemed non-eligible for all 3 trials. 50% of eligible infants were enrolled in at least one trial. 0.72% of infants were excluded due to death prior to 12 hours. Mothers with enrolled infants were more likely to have public medical insurance and to be of Hispanic ethnicity and less likely to have a multiple gestation pregnancy (Table 1). Survival was 84.1% in the enrolled group and 81.1% in the eligible non-enrolled group (adjusted OR (aOR) 1.25(1.02,1.53), p=0.04,Table 2). There were no differences in survival without NDI (aOR 1.19(0.99,1.41), p=0.05,Table 2) or rates of the components of NDI (Table 3) between enrolled and eligible non-enrolled infants.

Conclusion(s): In a contemporary cohort of extremely preterm infants, enrollment in an RCT was associated with a 4% increase in survival. Of note, no trial had a survival benefit with intervention itself. Participation in comparative effectiveness RCTs requires protocolization of patient care and careful monitoring, which may provide benefit compared to routine clinical practice. Potential benefits of participating in RCTs should be part of discussions regarding individual and institutional participation in clinical research.

Table 1. Maternal and Infant Characteristics
*The P values for categorical outcome comparisons were obtained using Chi-square test and Fisher exact test. Nonparametric Wilcoxon test was used to obtain P-values for continuous outcome comparisons.

Table 2. Primary Outcome by Enrollment Status
*Neurodevelopmental Impairment, as defined by one of following: Bayley III Cognitive <85 (1 SD below the mean of 100), Bayley III Motor <85 (1 SD below the mean of 100), Gross Motor Function Classification System level ≥2(regardless of diagnosis of cerebral palsy), Bilateral hearing impairment +/- amplification, Bilateral blindness.
**Odds ratios compare Enrolled vs. Eligible, not Enrolled. Logistic regression was used to obtain the odds ratio. For the adjusted analysis the variables included in the model were center, gestational age, birth weight, antenatal steroids, sex, multiple gestation, maternal education, maternal ethnicity, and public insurance status.

Table 3. Components of Neurodevelopmental Impairment by Enrollment Status
*GMFCS: Gross Motor Function Classification System
**Odds ratios compare Enrolled vs. Eligible, not enrolled. Logistic regression was used to obtain the odds ratio. For the adjusted analysis the variables included in the model were center, gestational age, birth weight, antenatal steroids, sex, multiple gestation, mother’s education and public insurance, and ethnicity of the mother. The blindness and GMFCS ≥4 outcomes were not adjusted for center because of convergence issues.